The DOI matches its Crossref record; 281 of the 286 references it cites were found in a registry or an index; none of the 200 sources its claims cite is checked for support yet.
The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
Open accessAbstract
Alzheimer's disease (AD) is the 3rd most costly disease and the leading cause of dementia. It can linger for many years, but ultimately is fatal, the 6th leading cause of death. Alzheimer's disease (AD) is fatal and affected individuals can sometimes linger many years. Current treatments are palliative and transient, not disease modifying. This article reviews progress in the search to identify the primary AD-causing toxins. We summarize the shift from an initial focus on amyloid plaques to the contemporary concept that AD memory failure is caused by small soluble oligomers of the Aβ peptide, toxins that target and disrupt particular synapses. Evidence is presented that links Aβ oligomers to pathogenesis in animal models and humans, with reference to seminal discoveries from cell biology and new ideas concerning pathogenic mechanisms, including relationships to diabetes and Fragile X. These findings have established the oligomer hypothesis as a new molecular basis for the cause, diagnosis, and treatment of AD.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that soluble Aβ oligomers, rather than insoluble amyloid plaques, are the primary synaptotoxic agents causing early memory failure in Alzheimer’s disease. It synthesizes cell, animal, and human evidence linking oligomers to synaptic plasticity disruption, synapse loss, tau pathology, insulin resistance, and candidate therapeutic strategies.
Key findings
- Aβ oligomers inhibit long-term potentiation (LTP) within minutes without affecting baseline excitability, and memory loss in APP transgenic mice can be reversed by anti-Aβ antibodies without removing amyloid plaques.
- Oligomers accumulate in AD-affected human brain and in essentially all transgenic AD models examined; synthetic and brain-derived oligomers show biochemical identity, and oligomer size remains debated (dimers–tetramers vs. 12mers/24mers), with SDS-stable 12mers linked to memory failure in one model.
- Oligomers target synapses: >90% co-localization with post-synaptic marker PSD-95; 50–85% of hippocampal neurons bind oligomers while others are spared; binding is associated with tau hyperphosphorylation, insulin receptor redistribution, spine loss, and oxidative stress.
- AD is discussed as a brain-specific form of diabetes (“type 3 diabetes”): Aβ oligomers induce insulin resistance, and intranasal insulin improves cognition in early AD at higher doses, consistent with insulin resistance.
Methods
- Narrative review of the literature, not a primary experimental study; it synthesizes findings from cell biology, animal models, human AD brain/CSF, and human genetics.
- Evidence discussed includes synthetic and brain-derived Aβ oligomers, transgenic mouse/rat/C. elegans/Drosophila models, electrophysiology (LTP/LTD), imaging, biochemical assays, and human clinical/ biomarker studies.
- Main analysis is qualitative synthesis; Tables 2 and 3 summarize synapse-specific and more generalized neuronal effects of Aβ oligomers.
Limitations
- Stated: the pathogenic oligomer size is uncertain; detection is limited by SDS-PAGE/Western blot, antibody choice, heat denaturation, and detergent; not all oligomers are toxic; nomenclature is confusing; why toxic oligomers accumulate in sporadic AD is largely unknown; intracellular vs. extracellular localization is unresolved; PrPC involvement is debated; synthetic oligomers can clump at high concentrations.
- Stated: published studies use different oligomer preparations, concentrations, incubation times, brain regions, and culture maturation stages, complicating comparison.
- Evident: as a narrative review, it lacks a systematic search strategy, formal quality appraisal, or meta-analysis, and presents an author-framed argument favoring the oligomer hypothesis.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 200 cited sources checked · 0 supported · 0 flagged
In the paper
“A classic study by Terry, Masliah and colleagues subsequently confirmed that synapse loss is the best pathological correlate of Alzheimer’s dementia (Terry et al., 1991).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Amyloid and nerve cell death are not the primary disease-causing pathologies
What the sources say
- Not checked yetcites Terry et al., 1991 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Amyloid in fact is a poor correlate of disease state in AD models as in humans (Terry et al., 1991),”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Amyloid and nerve cell death are not the primary disease-causing pathologies
What the sources say
- Not checked yetcites Terry et al., 1991 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Dot immunoblots of soluble extracts from human brain show major increases in oligomers in AD-affected tissue (Gong et al., 2003; Kayed et al., 2003; Lambert et al., 2001).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Most importantly, these amyloid-free Aβ oligomers were potent CNS neurotoxins.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Memory loss is a disruption of synaptic plasticity: the oligomer hypothesis
What the sources say
- Not checked yetcites Lambert et al., 1998 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Its clinical relevance has been established by evidence that equivalent oligomers accumulate in AD-affected human brain and animal AD models.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIn the paper
“Mucke and colleague found that synapse loss does not require the presence of amyloid deposits (Mucke et al., 2000).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Amyloid and nerve cell death are not the primary disease-causing pathologies
What the sources say
- Not checked yetcites Mucke et al., 2000 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Recent findings by Bateman and colleagues show that clearance of Aβ in AD patients is reduced by 30% (Mawuenyega et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Why do toxic oligomers accumulate?
What the sources say
- Not checked yetcites Mawuenyega et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Recent evidence suggests that insulin resistance, a hallmark of diabetes, develops in Alzheimer’s brains (, 2000; Craft et al., 1999; de la Monte, 2009; Moroz et al., 2008; Pedersen and Flynn, 2004; Razay and Wilcock, 1994; Watson and Craft, 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In hippocampal slices, synthetic oligomers cause rapid LTP inhibition (Barghorn et al., 2005; Fa et al., 2010; Jurgensen et al., 2011; Lambert et al., 1998; Nimmrich et al., 2008; Rammes et al., 2011; Wang et al., 2002).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“At the cellular level, deficient insulin signaling results in impaired removal of Aβ (Plum et al., 2005) and Aβ oligomers from the extracellular milieu (Zhao et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Why do toxic oligomers accumulate?
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“as have the related predictions that oligomers cause dysfunctional trafficking of ionotropic glutamate receptors and metabotropic glutamate receptors (Gong et al., 2003; Lacor et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“It is now known that a large variety of amyloidogenic peptides and proteins that are disease-associated make soluble cytotoxic oligomers.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
What the sources say
- Not checked yetcites Ferreira et al., 2007 source
- Not checked yetcites Klein, 2006
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Small oligomers obtained from AD-affected human brain also are active in plasticity assays (Barry et al., 2011; Klyubin et al., 2008; Li et al., 2011).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Synthetic and brain-derived oligomers appear structurally equivalent, consistent with the ability of conformation sensitive antibodies generated against oligomers formed in vitro to bind oligomers formed in situ.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Disruption of functional plasticity includes LTD, which is promoted, not inhibited (Shankar et al., 2008; Wang et al., 2002).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Somewhat surprisingly, acutely elevated oligomer levels have been noted after exposure to general anesthetics (Eckenhoff et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Why do toxic oligomers accumulate?
What the sources say
- Not checked yetcites Eckenhoff et al., 2004 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In an important developmental analysis, Lesne, Ashe and colleagues showed memory failure coincides with extracellular accumulation of SDS-stable12mers (Lesne et al., 2006).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
What the sources say
- Not checked yetcites Lesne et al., 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Involvement of the 12mer was validated by direct tests in which immuno-isolated 12mers injected into brains of wild-type rats caused impairment of spatial memory.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
What the sources say
- Not checked yetcites Lesne et al., 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Supporting this idea, AD-like changes have been observed in experimental models of insulin resistance, including animals fed a high fat diet or receiving intracerebral or IP injections of streptozotocin (Cao et al., 2007; Labak et al., 2010; Lester-Coll et al., 2006; Ma et al., 2009; Pratchayasakul et al., 2011; Tong et al., 2009; Zhang et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Further support was provided by studies in AD transgenic mice, in which hyperinsulinemia develops in parallel to accumulation of Aβ deposits and cognitive impairment (Pedersen and Flynn, 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites Pedersen and Flynn, 2004
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Experimentally-induced diabetes moreover causes accelerated cognitive failure in AD mouse models (Cao et al., 2007; Ho et al., 2004; Plaschke et al., 2010; Wang et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“The impact of oligomers is in harmony with recent findings that clusterin, which prevents amyloid formation and promotes oligomer formation, is an AD risk factor (Harold et al., 2009; Lambert et al., 2009; Thambisetty et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Memory loss is a disruption of synaptic plasticity: the oligomer hypothesis
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings have established the oligomer hypothesis as a new molecular basis for the cause, diagnosis, and treatment of AD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the disease-initiating pathology does not appear to be nerve cell death but rather an oligomer-induced disruption of the mechanisms of synaptic plasticity.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Early AD is largely a disease of memory formation, and memory dysfunction is the primary symptom bringing patients to physicians.
- Rests on an assumption: AD can be attributed to a single disease-initiating cytotoxin, albeit one likely elicited by multiple factors.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Evidence is presented that links Aβ oligomers to pathogenesis in animal models and humans, with reference to seminal discoveries from cell biology and new ideas concerning pathogenic mechanisms.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cytotoxicity of oligomers thus has emerged as a new basis for understanding pathogenic mechanisms in an array of degenerative diseases.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“expression of the ApoE4 allele, a major risk factor for sporadic AD (Corder et al., 1993; Schmechel et al., 1993; Strittmatter et al., 1993), may be involved.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Why do toxic oligomers accumulate?
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The oligomer hypothesis of AD memory failure, initially proposed based on the finding that synthetic oligomers inhibit LTP in hippocampal slices, is now supported by strong in situ evidence.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“This led to the intriguing notion that a form of brain-specific diabetes, also referred to as type 3 diabetes, develops in AD (de la Monte and Wands, 2005; Steen et al., 2005).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites de la Monte and Wands, 2005
- Not checked yetcites Steen et al., 2005 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The conclusion that oligomers are neurologically active is firmly established for synthetic and metabolically derived oligomers (i.e., obtained from AD brain extracts or from cells transfected with human APP).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“For example, individuals with type2 diabetes have an elevated AD risk (Luchsinger, 2008).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Why do toxic oligomers accumulate?
What the sources say
- Not checked yetcites Luchsinger, 2008 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, those oligomers that are toxic appear germane to the disease process, likely at its earliest stages.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The ability of synthetic oligomers to mimic the structure and activity of brain-derived species validates their use for experimentation.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In a recent and surprising twist in the Alzheimer field, clinical studies have revealed that type 2 diabetes patients are at higher risk of developing AD (for reviews, see (Carlsson, 2010; Kopf and Frolich, 2009; Riederer et al., 2011)).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As presented next, oligomers can also be linked to the major facets of AD neuropathology.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Oligomers thus arguably can account for the primary aspect of dementia in early AD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Early AD is largely a disease of memory formation, and memory dysfunction is the primary symptom bringing patients to physicians.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As a result, brain insulin signaling, which plays important roles in learning and memory (see below), is thought to be impaired in AD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“levels of brain insulin and insulin receptors (IRs) are lower in AD (Frolich et al., 1998; Rivera et al., 2005).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Recent results show that Aβ oligomers further impact insulin signaling by inducing serine phosphorylation of the insulin receptor substrate (IRS-1) (Bomfim, De Felice and collaborators, submitted).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites Bomfim, De Felice and collaborators, submitted
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Removal of IRs from the surface of neurons was subsequently verified in AD brains (Moloney et al., 2010), establishing the pathophysiological significance of the initial cell-based findings.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites Moloney et al., 2010 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“it is now clear that CNS insulin signaling is important for many aspects of neuronal survival and function (Broughton and Partridge, 2009; de la Monte and Wands, 2005; Reagan, 2007; Zhao and Alkon, 2001; Zhao et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insulin signaling in ADDL-attacked neurons thus is effectively blocked by the combined effect of internalization of IRs and aberrant serine phosphorylation of IRS-1.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“all mouse, rat, and invertebrate transgenic AD models show oligomers that are abundantly intracellular (Oakley et al., 2006; Oddo et al., 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“human subjects have been found to respond to CNS insulin signaling stimulation with enhanced verbal memory performance (Reger et al., 2008a).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites Reger et al., 2008a
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A factor that likely contributes to this intracellular abundance in the models is the excessively high level of Aβ fostered by the transgenes.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The beneficial effect of insulin in AD may derive, at least in part, from an acute decrease in ADDL synaptotoxicity.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“it was recently shown that insulin ameliorates Aβ oligomer-induced inhibition of LTP (Lee et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites Lee et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“These assays, which can be many orders of magnitude more sensitive than ELISAs, have established an AD-dependent accumulation of oligomers in human CSF (Fukumoto et al., 2010; Gao et al., 2010; Georganopoulou et al., 2005; Haes et al., 2005).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Neuronal IRs are involved in diverse brain functions including synapse plasticity, learning and memory (Chiu et al., 2008; Craft et al., 1996; Kern et al., 2001; Lee et al., 2005; Park et al., 2000).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, impairment in insulin signaling instigated by Aβ oligomers may be a central mechanism by which memory deficits develop in the earliest stages of AD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Extracellular occurrence of oligomers is consistent with the rapid outpouring of Aβ, and perhaps small oligomers, into brain interstitial fluid, measured by microdialysis in mouse models and humans (Cirrito et al., 2005; Kang et al., 2007; Kang et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Evidence indicates, in fact, that a dynamic equilibrium exists between intracellular and extracellular oligomers (Oddo et al., 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
- Not checked yetcites Oddo et al., 2003 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“In the E693Delta APP mutation discovered in a Japanese kindred (Nishitsuji et al., 2009), the presence of intracellular oligomers is essentially identical in patients and in the transgenic mouse model (Tomiyama et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“this AD phenotype and its mouse model manifest only oligomers, no amyloid plaques.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“High levels of somatic expression found in transgenic mice may mask any peri-somatic distribution.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Attachment of brain-derived oligomers shows a highly punctate nature.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“early studies showed that binding is lost upon controlled trypsin treatment of neurons (Lambert et al., 1998).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Lambert et al., 1998 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Oligomers show > 90% co-localization with the post-synaptic marker PSD-95 (Lacor et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
- Not checked yetcites Lacor et al., 2004 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“The same binding specificity and punctate pattern is observed for synthetic oligomers, particularly those greater than 50 kDa (Lacor et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
- Not checked yetcites Lacor et al., 2004 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“oligomer binding is significantly reduced in PrPC knock-out cells (Lauren et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Lauren et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“it is clear that oligomers are not abundant in the soma.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Cultured hippocampal neurons incubated with brain-derived oligomers show patterns that recapitulate the in situ distribution (Gong et al., 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
- Not checked yetcites Gong et al., 2003 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“These findings suggest that PrPC is involved in synaptic binding and synaptotoxicity of Aβ oligomers (Gimbel et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Gimbel et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“other studies have shown that PrP-expressing and PrP-knockout mice are equally susceptible to long-term memory impairment induced by Aβ oligomers (Balducci et al., 2010; Calella et al., 2010)”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“ADDL binding to synapses displays saturable kinetics (Renner et al., 2010)”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Renner et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Double-labeling with synaptophysin or FM463 establishes this localization to be at functional synapses (Renner et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
- Not checked yetcites Renner et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Significantly, the sites at which oligomers accumulate in culture comprise synapses, consistent with the rapid and specific effects seen on LTP and LTD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“High resolution confocal imaging confirms accumulation of oligomers at dendritic spines (Lacor et al., 2007).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
- Not checked yetcites Lacor et al., 2007 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, mounting and convincing evidence indicates that interaction of Aβ oligomers with synaptic membranes is mediated by cell surface proteins that act as toxin receptors.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Aβ oligomers bind to and trigger subsequent proteasomal degradation of the receptor tyrosine kinase EphB2.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Cisse et al., 2011 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“NMDARs are not down-regulated in insulin-treated neurons, despite decreases in ADDL binding sites induced by insulin (Decker et al., 2010a).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Decker et al., 2010a
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Co-immunoprecipitation and photoactivated amino acid cross-linking studies indicated that Aβ oligomers interact with complexes containing the GluR2 subunit of AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate) receptors”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Zhao et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“supporting the notion that, at least in part, the deleterious effects of Aβ oligomers on plasticity are independent of PrPC (Kessels et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Kessels et al., 2010 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“pharmacological inhibition or removal of surface AMPA receptors reduced oligomer binding to neurons (Zhao et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Zhao et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“oligomer binding is virtually abolished in dendrites of NMDAR knock-down neurons (Decker et al., 2010a).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Decker et al., 2010a
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Frizzled-mediated Wnt/β-catenin signaling has been shown to play an important role in synaptic plasticity (Chen et al., 2006; Varela-Nallar et al., 2010; Varela-Nallar et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“EphB2 receptor levels are reduced in parallel with NMDAR levels in ADDL-treated hippocampal neurons (Lacor et al., 2007).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Lacor et al., 2007 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly enough, however NMDARs do not appear to be directly responsible for ADDL binding.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Aβ oligomers were recently shown to cause a rapid increase in surface exposure and clustering of PrPC in hippocampal neurons and cell lines (Caetano et al., 2011).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Caetano et al., 2011 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“single particle tracking of quantum dot-labeled Aβ oligomers has demonstrated the participation of metabotropic glutamate receptors (mGluR5) in oligomer binding and clustering at synapses (Renner et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Renner et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In hippocampal cultures, between 50% and 85% of the neurons bind Aβ oligomers, while the others are spared.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NMDARs thus are specifically required for pathogenic oligomer binding to dendrites.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“the ADDL-attacked and ADDL-spared neurons exhibit similar levels of surface NMDARs (Decker et al., 2010a).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Decker et al., 2010a
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Receptor downregulation has been extended to other plasticity-associated receptors, including EphB2 receptors (Lacor et al., 2007), AMPA-Rs (Jurgensen et al., 2011; Zhao et al., 2010), and insulin Rs (Zhao et al., 2008).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both PrPC and NMDARs are thus poised to act as platforms that drive the assembly of a multi-protein complex responsible for the accumulation of synaptotoxic ADDL clusters.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“NMDA-R down-regulation appears to explain why glutamate stimulation of the CREB pathway is impaired by oligomers (Tong et al., 2001; Vitolo et al., 2002).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“One rapid consequence is an aberrant expression of Arc (Activity-Regulated Cytoskeletal associated protein; (Lacor et al., 2004)).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Lacor et al., 2004 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“This prediction was first confirmed for NMDA-Rs (Lacor et al., 2004; Lacor et al., 2007; Snyder et al., 2005).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At synapses, the relatively diffusible complex between Aβ oligomers and mGluR5 (or other component) becomes trapped in a larger, diffusion-restricted complex whose assembly is organized by key synaptic proteins. These “organizers” likely include NMDARs and PrPC”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“pharmacological experiments indicate involvement of CaMKII and casein kinase II (De Felice et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites De Felice et al., 2009 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“These receptor pathologies discovered in cell culture have been confirmed in tg-mouse models and human AD brain (Cisse et al., 2011; Moloney et al., 2010).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Synaptically controlled transient expression of Arc is essential for LTP and memory formation (Guzowski et al., 2000; Kelly and Deadwyler, 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Guzowski et al., 2000 source
- Not checked yetcites Kelly and Deadwyler, 2003
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Excessive Ca++ caused by Aβ oligomers is partially inhibited by NMDA-R antagonists, including the clinically approved AD drug Namenda (De Felice et al., 2007).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites De Felice et al., 2007 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whether oligomers act directly on mGluR5 receptors, like antibodies, or indirectly through interactions with other scaffolding molecules, it appears that it is the clustering that causes synapto-toxic mGluR5 hyperactivity.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The profound impact of oligomers on mGluR5 mobility and the induced formation of mGluR5 clusters appears germane to the mechanism by which Ca++ is elevated to synapto-toxic levels.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“mGluR5 stimulation is known to enhance NMDA-R responses (Blaabjerg et al., 2001).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Blaabjerg et al., 2001 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“protection also is afforded by antagonists of metabotropic mGluR5 receptors (Rammes et al., 2011; Renner et al., 2010; Wang et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“FMRP participates in the trafficking and expression of mRNAs that target spines.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“Synapse deterioration in tg-mice is prevented by ICV injections of oligomer-specific antibodies (Chauhan, 2007; Oddo et al., 2006).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“This reduction is sufficient to inhibit synapse deterioration (Lacor et al., 2007).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Lacor et al., 2007 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Excessive mGluR5 activity is prevented by FMRP itself through a negative feedback loop.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“As in oligomer-exposed neurons, neurons in Fragile X ectopically overexpress Arc (Zalfa et al., 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
What the sources say
- Not checked yetcites Zalfa et al., 2003 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“In healthy neurons, Ca++ mobilization by mGluR5 leads to dephosphorylation of FMRP, relieving FMRP repression of translation (Bear et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
What the sources say
- Not checked yetcites Bear et al., 2004 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Underlying the mechanism of synapse deterioration is hyperactive glutamatergic signaling.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“the recent finding that mGluR5 is implicated in the toxic clustering of Aβ oligomers at synapses and the ensuing aberrant calcium signaling (Renner et al., 2010) suggests that selective mGluR5 inhibitors may hold potential to block oligomer-induced synapse dysfunction.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Promise of therapeutics
What the sources say
- Not checked yetcites Renner et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This impact of oligomers would be functionally equivalent to eliminating FMRP protein.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although by no means identical, the behavioral and cognitive abnormalities in AD and Fragile X appear to have common roots at the molecular and synaptic level.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“mGluR5, through its physiological inactivation of FMRP, has been reported to stimulate translation of APP (Westmark and Malter, 2007).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
What the sources say
- Not checked yetcites Westmark and Malter, 2007 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 69
- Probably not a substantial claim. 20
In the paper
“Dodart, Paul and colleagues found that memory loss was reversed in APP tg-mice injected with antibodies against Aβ and that this reversal, moreover, did not require removal of amyloid plaques (Dodart et al., 2002).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Amyloid and nerve cell death are not the primary disease-causing pathologies
What the sources say
- Not checked yetcites Dodart et al., 2002 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Investigation into the action of clusterin by Lambert, Klein and colleagues established that, concomitant with inhibition of amyloid formation, clusterin promotes accumulation of soluble Aβ oligomers (Lambert et al., 1998).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Memory loss is a disruption of synaptic plasticity: the oligomer hypothesis
What the sources say
- Not checked yetcites Lambert et al., 1998 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“some neuropathologists rejected the hypothesis, emphasizing that a poor correlation exists between plaque load and cognitive function (Terry et al., 1994).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis
What the sources say
- Not checked yetcites Terry et al., 1994
Tests✗ Asserted: fails✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. The authors may not put it forward as true.
In the paper
“With chronic exposure, neurons ultimately were killed. Death was selective for subpopulations of vulnerable neurons and was prevented by knockout of Fyn, a protein tyrosine kinase linked to NMDA receptor signaling.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Memory loss is a disruption of synaptic plasticity: the oligomer hypothesis
What the sources say
- Not checked yetcites Lambert et al., 1998 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Based on a central role for impaired signaling, the oligomer hypothesis predicted that early memory loss should be reversible. This prediction was confirmed in the transgenic mouse experiments mentioned above (Dodart et al., 2002; Kotilinek et al., 2002).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Memory loss is a disruption of synaptic plasticity: the oligomer hypothesis
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“oligomers were found to inhibit functional synaptic plasticity (Lambert et al., 1998). Long-term potentiation (LTP) was inhibited within minutes. This rapid loss of LTP, measured in rat brain slices and in situ in mice, occurred without impact on baseline excitability, indicating impairment of signaling rather than degeneration.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Memory loss is a disruption of synaptic plasticity: the oligomer hypothesis
What the sources say
- Not checked yetcites Lambert et al., 1998 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Immunohistochemistry confirms that oligomers associate with neurons, accumulating very early in disease progression (Lacor et al., 2004), in loci distinct from amyloid deposits (Kayed et al., 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“At present it is uncertain whether one class is more germane to pathogenesis than another.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Remarkably, at sub-nanomolar doses, the effect on LTP is reversed, and Aβ markedly enhances LTP. Discovered by Arancio and colleagues in a detailed analysis (Puzzo et al., 2008), enhancement occurs over a narrow range of concentrations and is associated with presynaptic activation of alpha7 nicotinic receptors.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
What the sources say
- Not checked yetcites Puzzo et al., 2008 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“And in fact, not all oligomers are toxic, even those oligomers of a given size. Subtle conformation changes affect toxicity and immunoreactivity (Chromy et al., 2003; Pitt et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Traumatic brain injury also is associated with acutely elevated levels in CSF, with a positive correlation between oligomer levels and severity of sequelae (David Brody, MP Lambert, and WL Klein, unpublished).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Why do toxic oligomers accumulate?
What the sources say
- Not checked yetcites David Brody, MP Lambert, and WL Klein, unpublished
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In FAD, metabolic effects of mutations promote increased levels of total Aβ, or increased Aβ42 to Aβ40 ratio (Borchelt et al., 1996; Citron et al., 1992), conditions that favor oligomerization.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Why do toxic oligomers accumulate?
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“More generalized neuronal impacts of Aβ oligomers (Table 3) include Ca2+ dyshomeostasis, oxidative stress and mitochondrial damage, proteasome inhibition, tau accumulation and hyperphosphorylation, impairment of fast axonal transport, ER stress, inhibition of the proteasome, cell cycle re-entry and, ultimately, cell death.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Synapse-specific and other pathological cellular consequences of ADDL binding to neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The discovery that memory failure in tg mice coincides with the appearance of SDS-stable 12mers is compelling in situ evidence that this species is pathogenic (Lesne et al., 2006).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Clinical relevance: build up of toxic oligomers in AD and AD animal models
What the sources say
- Not checked yetcites Lesne et al., 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Relative levels of Aβ42 to Aβ40 appear to influence the mechanism of oligomerization, with higher levels of Aβ40 in normal individuals likely impeding formation of stable toxic oligomers (Giuffrida et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Why do toxic oligomers accumulate?
What the sources say
- Not checked yetcites Giuffrida et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Tg-mouse AD models manifest a spontaneous age-onset impairment of LTP (Gong et al., 2004) that presumably is linked to impaired performance in memory tests (Arendash et al., 2001).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neurological consequences: Oligomers impair synapse plasticity and learning
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Synapse-specific effects of Aβ oligomers (Table 2) include alterations in neurotransmitter (glutamate/D-serine) levels, down-regulation (due to abnormal trafficking or degradation) of plasticity-related receptors at the plasma membrane, altered plasticity (inhibition of long term potentiation and/or facilitation of long term depression), cytoskeletal abnormalities and synapse loss.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Synapse-specific and other pathological cellular consequences of ADDL binding to neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Memory loss, beginning early in the disease, was attributed to oligomer-induced disruption of synaptic plasticity, with later stages of dementia attributed to oligomer-induced cellular degeneration and death.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Memory loss is a disruption of synaptic plasticity: the oligomer hypothesis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Early AD is largely a disease of memory formation, and memory dysfunction is the primary symptom bringing patients to physicians.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, while Aβ is essential for memory loss, the fibrillar Aβ in amyloid deposits is not the agent.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Amyloid and nerve cell death are not the primary disease-causing pathologies
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We summarize the shift from an initial focus on amyloid plaques to the contemporary concept that AD memory failure is caused by small soluble oligomers of the Aβ peptide, toxins that target and disrupt particular synapses.”
- Also stated in: § Abstract · plain
“We summarize here why attention has shifted away from amyloid plaques as the toxic agents of AD to the contemporary concept that memory failure is caused by small soluble oligomers of the Aβ peptide, toxins that target and disrupt particular synapses.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Early AD is largely a disease of memory formation, and memory dysfunction is the primary symptom bringing patients to physicians.
- Rests on an assumption: AD can be attributed to a single disease-initiating cytotoxin, albeit one likely elicited by multiple factors.
- Also stated in: § Abstract · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The conclusion that Aβ oligomers can be neurologically significant toxins, possibly the most important ones for AD, is now supported by more than a decade of further investigation, with over 1,000 papers addressing the oligomer hypothesis.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Memory loss is a disruption of synaptic plasticity: the oligomer hypothesis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: AD can be attributed to a single disease-initiating cytotoxin, albeit one likely elicited by multiple factors.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it now appears the most pathogenically relevant Aβ-derived toxins are small soluble oligomers, not readily detected.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: AD can be attributed to a single disease-initiating cytotoxin, albeit one likely elicited by multiple factors.
In the paper
“The hypothesis attributed dementia to nerve cell death caused by the toxicity of large insoluble amyloid fibrils.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis
What the sources say
- Not checked yetcites Hardy and Higgins, 1992 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In conclusion, besides directly affecting memory-related processes, the various impacts of Aβ oligomers on neurons have the potential to account for major facets of AD neuropathology (e.g., tau hyperphosphorylation, oxidative stress, synapse loss), supporting the concept that Aβ oligomers provide a unifying mechanism for initiation of AD pathogenesis.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Synapse-specific and other pathological cellular consequences of ADDL binding to neurons
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: AD can be attributed to a single disease-initiating cytotoxin, albeit one likely elicited by multiple factors.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Serine phosphorylation precludes tyrosine phosphorylation of IRS-1, blocking downstream insulin signaling.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Physiologically, IRS-1 is phosphorylated at tyrosine residues by the tyrosine kinase activity of the IR, which activates downstream signaling in the insulin pathway (Araki et al., 1994; White, 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“IRs are present in the brain, where they are abundantly distributed in synaptic membranes of the cerebral cortex and hippocampus (Abbott et al., 1999; Havrankova et al., 1981; Marks et al., 1990; Unger and Betz, 1998).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Aβ oligomers induce a striking redistribution of IRs, causing their internalization from dendritic membranes and accumulation in the cell body. This renders neurons insulin resistant (De Felice et al., 2009; De Felice et al., 2008; Zhao et al., 2008).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Brain insulin signaling declines with age (Frolich et al., 1998; , 1999; Hoyer, 1998; Rivera et al., 2005), the primary risk factor for AD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“an elevated risk for AD also exists in type 2 diabetes patients, who manifest deficient CNS insulin signaling (Matsuzaki et al., 2010; Ott et al., 1999; Toro et al., 2009; Watson and Craft, 2003), likely as a consequence of decreased insulin uptake into the brain following sustained peripheral hyperinsulinemia (Gerozissis et al., 1993; Kaiyala et al., 2000; Schwartz et al., 1990).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Internalization occurs by a mechanism mediated by casein kinase 2 (CK2) and Ca2+/calmodulin-dependent kinase 2 (CaMK II), which also are involved in ADDL-induced internalization of NMDA receptors (De Felice et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites De Felice et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The possible source of extracellular oligomers and how they interact with neurons in human brain are suggested by their peri-somatic localization, observed in early-stage disease (Figure 1, left; (Lacor et al., 2004)).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
- Not checked yetcites Lacor et al., 2004 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, physiological insulin signaling may play an important role in defending neurons against AD, suggesting the loss of CNS insulin signaling in aging and diabetes is a potential risk factor for AD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“When given to subjects with early AD, intranasal insulin also improves performance (Reger et al., 2008b) but only at higher doses, consistent with expected insulin resistance and suggesting possible involvement of additional mechanisms other than stimulation of plasticity.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites Reger et al., 2008b
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Aβ oligomers induce a marked removal of IRs from synapses, decreasing the responsiveness of nerve cells to insulin.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The insulin-sensitizing drug rosiglitazone, a PPAR-γ agonist, potentiates the ability of insulin to protect synapses against Aβ oligomers, while a cell-permeant inhibitor of the tyrosine kinase activity of the IR abrogates the protection by insulin.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“insulin itself blocks the pathological binding of Aβ oligomers and the resulting redistribution of IRs and synapse loss (De Felice et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
- Not checked yetcites De Felice et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the ability of antibodies to reverse intracellular tau and synapse pathology (Chauhan et al., 2008; Oddo et al., 2006) and to provide cognitive benefits (Hillen et al., 2010; Takamura et al., 2011).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“stimulation of insulin signaling also protects against accumulation of hyperphosphorylated tau (Escribano et al., 2010), a pathological hallmark of AD that is induced by Aβ oligomers (De Felice et al., 2008).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The mechanism of protection does not involve direct competition between Aβ oligomers and insulin for a common binding site on the neuronal surface. Rather, it consists of an IR signaling-dependent down-regulation of neuronal ADDL binding sites.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Neuronal insulin resistance induced by Aβ oligomers: AD as a novel form of brain-specific diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Clustering of oligomers at synapses, moreover, shows a cause-and-effect relationship with characteristic Alzheimer neuropathologies. AD type tau hyperphosphorylation (De Felice et al., 2008), redistribution of insulin receptors (De Felice et al., 2009; Zhao et al., 2008), spine loss (Lacor et al., 2007) and oxidative stress (De Felice et al., 2007; Decker et al., 2010a) are manifest exclusively in”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, the peri-somatic distribution in human brain is evident in the complete absence of amyloid plaques, indicating oligomer pathology occurs early in the disease process.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As expected, the pattern of binding depends on cell maturation.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These oligomer-targeted neurons are distributed sparsely, indicating oligomers might originate within the cells they surround (Figure 1, right).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It can be concluded that oligomers are gain-of-function pathogenic ligands that target and disrupt signaling at particular synapses, a specificity that may explain why early AD is a disease of memory.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Aβ oligomers bind with nanomolar affinity to cellular prion protein (PrPC) and that anti-PrP antibodies reduce oligomer binding to neurons and rescue synaptic plasticity (Lauren et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Lauren et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Significantly, some neurons are targeted while others are not, establishing clear-cut specificity.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Initiating mechanisms – the targets are synapses
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“EphB2 receptors interact functionally and physically with NMDARs at synapses”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Other putative receptors/co-receptors involved in neuronal binding of Aβ oligomers include the p75 neurotrophin receptor (p75NTR) (Knowles et al., 2009), the receptor for advanced glycation end products (RAGE) (Sturchler et al., 2008), nicotinic acetylcholine receptors (Magdesian et al., 2005) and Frizzled (Magdesian et al., 2008).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggest that ADDL binding to synapses may involve the assembly of a multi-protein receptor whose assembly is promoted by NMDARs and likely involves other participants, including PrPC.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations indicate that NMDARs are necessary but not sufficient for ADDL binding”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“This suggests that initial ADDL binding recruits more PrPC molecules (presumably by exocytosis of vesicles located proximal to the plasma membrane; (Caetano et al., 2011)) to form a higher order complex that may initiate toxic signaling at”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Caetano et al., 2011 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“NMDARs co-immunoprecipitate with Aβ oligomers from detergent-extracted oligomer-treated rat synaptosomal membranes, and an N-terminal anti-NR1 antibody markedly reduced oligomer binding to dendrites (De Felice et al., 2007).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites De Felice et al., 2007 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“NMDAR knock-down also abrogates neuronal oxidative stress induced by Aβ oligomers, which is mediated by aberrant activation of NMDARs (De Felice et al., 2007).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites De Felice et al., 2007 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A second prediction based on altered Arc expression is that oligomers would induce aberrant dendritic spine morphology, and this also has been confirmed in culture and in situ (Lacor et al., 2007; Ma et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Lacor et al., 2007 source
- Not checked yetcites Ma et al., 2009
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although receptors are lost from the surface, total levels are at first unchanged, indicating dysfunctional trafficking”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“What emerges from current evidence is that Aβ oligomers first bind to the neuronal plasma membrane at freely moving receptors, but lateral diffusion leads to interactions between Aβ oligomers and membrane proteins such as mGluR5 that ultimately target Aβ oligomers to synaptic sites.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Initially, Aβ oligomers diffused as if bound to an untethered protein. Within minutes, however, movement slowed and oligomers became immobilized, typically at active synapses labeled with FM4-64. The synaptic trapping of oligomers was accompanied by co-clustering and immobilization of mGluR5 metabotropic glutamate receptors.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Renner et al., 2010 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Because Arc is an actin binding protein, its aberrant expression was predicted to disrupt receptor trafficking (Lacor et al., 2004), which could consequently disrupt plasticity (Gong et al., 2003).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“explaining the finding that knocking-down these proteins or adding antibodies against their extracellular domains blocks the accumulation of ADDL clusters (“hotspots”) at synapses (De Felice et al., 2007; Decker et al., 2010a; Lauren et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Within minutes of exposure to oligomers, neurons show a localized over-expression of Arc, which later spreads ectopically throughout the dendrite.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Arc is an immediate early gene product that is translated from mRNA in dendritic spines (Bramham, 2008).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Bramham, 2008 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The mechanism of oligomer synapto-toxicity appears to be tied closely to accumulation of excessive levels of Ca++ (Marx, 2007), consistent with involvement of NMDA and mGluR5 receptors.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Marx, 2007 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interaction with Aβ oligomers could potentially dysregulate such signaling pathways, resulting in neurotoxicity.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“PrPC has been proposed to act as a cell-surface platform that orchestrates several physiological signaling pathways at the neuronal plasma membrane (for reviews, see (Linden et al., 2008; Martins et al., 2010)).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > How spines are targeted by Aβ oligomers – receptors, co-receptors, scaffolds and toxic clusters
What the sources say
- Not checked yetcites Linden et al., 2008 source
- Not checked yetcites Martins et al., 2010
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The consequent chronic mGluR5 activity would keep FMRP dephosphorylated and eliminate the ability of FMRP to repress mRNA translation.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Such aberrant spines also are seen in traumatic brain injury and prionoses (Fiala et al., 2002).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Fiala et al., 2002 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Fragile X also leads to hyperactivity in the protein phosphatase PP2a (Kim et al., 2008) which inactivates MAPK, an enzyme with impaired activity in oligomer-exposed neurons (Tong et al., 2001).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hyperactivity of mGluR5 receptors caused by oligomers is due to a clustering mechanism, as described earlier, and this receptor state hypothetically could be insensitive to negative feedback by FMRP.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Spines after short-term exposure to oligomers are long and spindly, resembling immature spines that express low levels of AMPA-Rs, as found early in development.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In the absence of FMRP, mGluR5 is hyperactive, with the consequences detailed above, and mGluR5 antagonists have been suggested as an approach to Fragile X treatment.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This mechanism is in many respects analogous to the clustering of receptors at immunological synapses during T cell activation (Douglass and Vale, 2005), with the fundamental difference that oligomer-induced clustering is toxic.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Douglass and Vale, 2005
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Its control of Arc is a prime example (Iacoangeli et al., 2008).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
What the sources say
- Not checked yetcites Iacoangeli et al., 2008 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Eventually, spines deteriorate and synapses are lost, consistent with low levels of Arc found in mature tg-mice (Chin et al., 2005).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
- Not checked yetcites Chin et al., 2005 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Additional synaptic pathologies instigated by oligomers also are present in Fragile X, including aberrant spine morphology, loss of NMDA and AMPA receptors, and elevated LTD (Bear et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
What the sources say
- Not checked yetcites Bear et al., 2004 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Fragile X is a developmental disorder caused by inability to express the regulatory protein FMRP.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Another actin binding protein found in spines, drebrin, also becomes greatly diminished in culture (Lacor et al., 2007) and in tg-mice (Calon et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Clustering can be elicited by mGluR5 antibodies, and antibody-induced clustering mimics the effects of oligomers in causing elevated Ca++ and synapse deterioration.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Oligomer-induced Ca++ elevation: Consequences and a novel triggering mechanism
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“there is also reason to believe that non-pharmacological approaches based on these novel findings might be beneficial to ameliorate AD symptoms (Schaeffer et al., 2009).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Promise of therapeutics
What the sources say
- Not checked yetcites Schaeffer et al., 2009 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Coupled with the potential of dendrites for activity-stimulated exocytosis (Kennedy et al., 2010), such a phenomenon could account for the “perineuronal deposits” of oligomers seen in Figure 1 (Lacor et al., 2004).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
What the sources say
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For example, exercise and a balanced diet might have positive effects on both peripheral and brain insulin signaling.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Promise of therapeutics
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One of the implications of this finding is that D1/D5 receptors may constitute a target for the development of novel approaches to combat synapse failure in AD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Promise of therapeutics
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In particular, the discovery that insulin resistance plays an important role in the pathogenesis of AD suggests that strategies aimed to bolster brain insulin signaling might be beneficial in preventing synapse failure and neuronal damage in AD.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Promise of therapeutics
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“dopaminergic neurotransmission, centrally implicated in the brain reward system and known to decline with aging (De Keyser et al., 1990), plays important roles in non-pharmacological strategies aimed to improve age-related cognitive decline, such as environmental enrichment and physical exercise (van Praag et al., 2000).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Promise of therapeutics
What the sources say
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Oligomer-induced hyperactivity of mGluR5 in Alzheimer’s disease would thus promote production of even more Aβ and oligomers.”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Comparison with another disorder of learning and memory: AD and Fragile X Syndrome show striking similarities
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“a connection has recently been established between dopaminergic signaling and AD, with demonstration that selective activation of D1/D5 dopamine receptors prevents pathological changes in synapse composition and function (including inhibition of LTP) induced by Aβ oligomers (Jurgensen et al., 2011).”
§ The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas > The original amyloid cascade hypothesis > Promise of therapeutics
What the sources say
- Not checked yetcites Jurgensen et al., 2011 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
Early AD is largely a disease of memory formation, and memory dysfunction is the primary symptom bringing patients to physicians.
“the symptom that first brings patients to a physician is a troubling inability to form new memories, and early AD is largely regarded as a disease of memory formation.”
The paper relies on this without support.
AD can be attributed to a single disease-initiating cytotoxin, albeit one likely elicited by multiple factors.
“This article reviews progress in the search for primary AD-causing toxins.”
“If we could regard AD as having a single disease-initiating cytotoxin (albeit one likely elicited by multiple factors), its action minimally must provide a basis for memory dysfunction.”
The authors state this as an assumption.
Aβ oligomers act from the extracellular milieu.
“A premise for investigating the effects of exogenous oligomers on memory and neuropathology is that oligomers presumably act from the extracellular milieu.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Thus, the production of Aβ is a complex process and accumulating evidence indicates that soluble Aβ oligomers, not Aβ plaques alone, are the disease-causing species that induce substantial neurotoxicity including synaptic dysfunction and behavioral impairment [see review in Ref. (138)].”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [138]
In the citing paper
“In vivo and in vitro studies support a direct relationship between OS and synaptic dysfunction in AD [18,86,87,88,89,90].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [88]
Citations
Cites
2 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769
RetractedPratchayasakul, W., Kerdphoo, S., Petsophonsakul, P., Pongchaidecha, A., Chattipakorn, N., & Chattipakorn, S. C. (2011) · Life Sciences · doi:10.1016/j.lfs.2011.02.003 · Cited by 206
RetractedAmyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404
Overdependence on degraded gist memory in Alzheimer's disease.
Gallo, D. A., Shahid, K. R., Olson, M. A., Solomon, T. M., Schacter, D. L., & Budson, A. E. (2006) · Neuropsychology · doi:10.1037/0894-4105.20.6.625 · Cited by 4,757
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291
Flagged first, then by citations
5 of the 286 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870
Self-citationBomfim, T. R., Forny‐Germano, L., Sathler, L. B., Brito‐Moreira, J., Houzel, J., Decker, H., Silverman, M. A., Kazi, H., Melo, H. M., McClean, P. L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci57256 · Cited by 849
Self-citationRajmohan, R., & Reddy, P. H. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160612 · Cited by 730
Felice, F. G. D., & Ferreira, S. T. (2014) · Diabetes · doi:10.2337/db13-1954 · Cited by 676
Self-citationAmyloid β oligomers in Alzheimer’s disease pathogenesis, treatment, and diagnosis
Viola, K. L., & Klein, W. L. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1386-3 · Cited by 628
Self-citation
Metadata
- Authors
- Ferreira, S. T., & Klein, W. L.
- Affiliations
- Universidade Federal do Rio de Janeiro (BR)
- Northwestern University (US)
- Corresponding author
- Klein, William L.
- Venue
- Neurobiology of Learning and Memory
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 96
- Issue
- 4
- Pages
- 529-543
- ISSN
- 1074-7427 (ISSN-L)
- PMC
- PMC4390395
- OpenAlex
- W2051268743
- Cited by
- 442
- References
- 286
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 22 · 2023: 24 · 2022: 37 · 2021: 28 · 2020: 35 · 2019: 23 · 2018: 44 · 2017: 41 · 2016: 33 · 2015: 35 · 2014: 38 · 2013: 24 · 2012: 26
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Learning and Memory (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG022547, R01AG029460, R01AG018877)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta oligomers, memory loss, amyloid plaques, pathogenesis, diabetes mellitus, fragile X syndrome, animal models of Alzheimer's disease, Alzheimer's disease treatment
- MeSH terms
- Alzheimer Disease, Brain, Humans, Memory Disorders, Neurons, Synapses, Amyloid beta-Peptides, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
