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Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein
Open accessAbstract
Inability to form new memories is an early clinical sign of Alzheimer’s disease (AD). There is ample evidence that the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Aβ are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Aβ−mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Aβ 1–42 oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ 1–42 fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody. It has been suggested that the cellular prion protein (PrP C ) mediates the impairment of synaptic plasticity induced by Aβ. We confirmed that Aβ 1–42 oligomers interact with PrP C , with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Aβ 1–42 oligomers are responsible for cognitive impairment in AD and that PrP C is not required.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Acute intracerebroventricular injection of synthetic Aβ1–42 oligomers impaired consolidation of long-term object-recognition memory in mice, whereas fibrils and freshly dissolved peptide did not. Although Aβ oligomers bound cellular prion protein (PrPC) with high affinity, PrP-expressing and PrP knockout mice were equally susceptible, indicating PrPC is not required for this memory impairment.
Key findings
- Synthetic Aβ1–42 oligomers (estimated 10–50 nM) impaired long-term recognition memory; mature fibrils and freshly dissolved Aβ did not.
- The oligomer-induced deficit was reversible: memory had fully recovered 10 days after injection without further Aβ, and was completely prevented by i.c.v. pretreatment with 0.25 μg/2 μL of the anti-Aβ antibody 4G8.
- Aβ oligomers bound PrPC with high affinity (Kd ≤20 nM monomer equivalent), but Prnp 0/0 mice were as susceptible as Prnp +/+ mice to oligomer-induced memory impairment; oligomers were also toxic to both Prnp +/+ and Prnp 0/0 hippocampal neurons in vitro.
- Oligomers disrupted memory encoding/consolidation but not retrieval: injection before familiarization prevented memory, whereas injection before the test phase did not.
Methods
- Male C57BL/6 mice, 7–8 weeks old, received acute i.c.v. injections of synthetic Aβ1–42 preparations and were tested in the novel-object recognition task; Prnp 0/0 and Prnp +/+ mice were compared.
- Aβ1–42 oligomers, fibrils, and initial-state peptide were characterized by atomic force microscopy and size exclusion chromatography before behavioral testing.
- Binding to PrPC was measured by surface plasmon resonance using brain homogenates and anti-PrP antibodies; primary hippocampal neuron cultures were treated with 1–3 μM oligomers for 72 h and survival measured by MTT assay. Statistical analysis used ANOVA with post hoc tests.
Limitations
- The paper states that one limitation is the use of oligomeric Aβ preparations not proven identical to those found in AD patient brains.
- Evident from the text: object recognition memory is associated more with perirhinal cortex than hippocampus, so the behavioral model may not fully align with hippocampal LTP studies.
- Evident from the text: the study used only male C57BL/6 mice and a single behavioral task, and it does not establish the mechanism linking Aβ oligomer binding to PrPC with memory impairment.
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Claims the paper makes
20 Own result · 18 Not checked yet · 11 Own interpretation · 2 No basis given · 1 Own method
A result the paper reports from its own data — 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 deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody.”
- Also stated in: § Results · plain
“After 10 days, with no further Aβ injection, the memory deficit had fully recovered (Fig. 3A).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — 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, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment.”
- Also stated in: § Results · plain
“We found that Prnp 0/0 mice were as susceptible as Prnp +/+ mice to oligomer-induced memory impairment (Figs. 2B and 4A).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we report that, in mice, acute intracerebroventricular injections of synthetic Aβ1–42 oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ1–42 fibrils and freshly dissolved peptide did not.”
- Also stated in: § Results · plain
“Aβ oligomer–injected mice were unable to distinguish the new object, with no significant difference in the percentage of time spent investigating the two (Fig. 2A), and a discrimination index significantly lower than vehicle-injected mice (Fig. 2B).”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — 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 confirmed that Aβ1–42 oligomers interact with PrPC, with nanomolar affinity.”
- Also stated in: § Results · plain
“The binding was dose dependent, with a dissociation constant (K d) of ≤20 nM monomer equivalent (Fig. 7 B and D).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — 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 deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody.”
- Also stated in: § Results · plain
“An i.c.v. injection of 0.25 μg/2 μL of 4G8, 5 min before the Aβ oligomers, completely prevented the memory impairment (Fig. 3B).”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but found no evidence that the two events are related.”
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An i.c.v. injection of 4G8 alone did not affect memory.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the basis of SEC, we estimated the actual oligomer concentration in this sample as 10–50 nM.”
- Also stated in: § Discussion · plain
“The effect was detectable at a nanomolar concentration of Aβ oligomers (10–50 nM).”
plain- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
A result the paper reports from its own data — 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 single i.c.v. injection of a nanomolar concentration of synthetic Aβ1–42 oligomers impairs memory consolidation within 24 h, suggesting that oligomers rapidly interfere with the synaptic activity necessary for the stabilization of new memories.”
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heat-denatured antibody, unable to bind Aβ, could not antagonize the effect of Aβ oligomers.”
hedged- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 14
- Probably not a substantial claim. 15
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas mature Aβ1–42 fibrils and freshly dissolved peptide did not.”
- Also stated in: § Results · plain
“Neither Aβ in the initial state nor the fibrils affected memory (Fig. 2 A and B).”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When Aβ initial state, oligomers or fibrils were assayed for their binding to PrPC, only Aβ oligomers bound PrPC specifically, and Aβ initial state and fibrils did not (Fig. 7 A and C).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mice injected 2 h before familiarization were unable to remember the object previously investigated, whereas mice injected 2 h before the test phase recalled the familiar object investigated the day before (Fig. 8).”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Preliminary data confirmed that the captured protein is actually PrPC, as no capture was detected when flowing brain homogenate from Prnp 0/0 mice (Fig. 6).”
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“PrPC binds synthetic Aβ oligomers with high affinity and plays a role in the oligomer-mediated inhibition of LTP (17).”
What the sources say
- Not checked yetcites [17] Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature. 2009;457:1128–1132. doi: 10.1038/nature07761. [DOI] [PMC free article] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“All of these processes are affected by Aβ oligomers in vitro, using primary neuronal cultures (12, 15, 36, 37).”
What the sources say
- Not checked yetcites [12] Shankar GM, et al. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci. 2007;27:2866–2875. doi: 10.1523/JNEUROSCI.4970-06.2007. [DOI] [PMC free article] [PubMed] [Google Scholar] source
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- Not checked yetcites [36] Hsieh H, et al. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron. 2006;52:831–843. doi: 10.1016/j.neuron.2006.10.035. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [37] Lacor PN, et al. Synaptic targeting by Alzheimer’s-related amyloid beta oligomers. J Neurosci. 2004;24:10191–10200. doi: 10.1523/JNEUROSCI.3432-04.2004. [DOI] [PMC free article] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably 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
“Several neuronal receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory, including the α-7-nicotinic (16), glutamatergic (39–40), and insulin (14) receptors.”
What the sources say
- Not checked yetcites [16] Snyder EM, et al. Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci. 2005;8:1051–1058. doi: 10.1038/nn1503. [DOI] [PubMed] [Google Scholar] source
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hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“These data indicate that Aβ oligomers acutely disrupt anterograde memory storage but do not interfere with its retrieval when the information has been properly stored.”
- Also stated in: § Discussion · plain
“Aβ oligomers inhibited the encoding/consolidation of information, without affecting its retrieval if properly stored.”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Discussion · plain
In the paper
“In an elegant study Lauren et al. (17) reported that PrPC mediates the Aβ oligomer-induced hippocampal synaptic plasticity impairment.”
What the sources say
- Not checked yetcites [17] Laurén J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature. 2009;457:1128–1132. doi: 10.1038/nature07761. [DOI] [PMC free article] [PubMed] [Google Scholar] source
plaindirect- Asserted: fails — The authors may not put it forward as true.
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Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it.
In the paper
“Because recognition memory is dependent on the medial temporal lobe including the hippocampus (25), we examined whether oligomer-mediated memory impairment was also related to PrPC expression.”
What the sources say
- Not checked yetcites [25] Squire LR, Wixted JT, Clark RE. Recognition memory and the medial temporal lobe: A new perspective. Nat Rev Neurosci. 2007;8:872–883. doi: 10.1038/nrn2154. [DOI] [PMC free article] [PubMed] [Google Scholar]
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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
“Unlike Aβ aggregates purified from biological sources, synthetic Aβ oligomers are chemically defined, and can be easily produced and biophysically characterized.”
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, some human and primate studies have shown that hippocampal lesions result in impaired object recognition (41, 42)”
What the sources say
- Not checked yetcites [41] Reed JM, Squire LR. Impaired recognition memory in patients with lesions limited to the hippocampal formation. Behav Neurosci. 1997;111:667–675. doi: 10.1037//0735-7044.111.4.667. [DOI] [PubMed] [Google Scholar]
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hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What 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
“These preparations, and freshly dissolved Aβ1−42 (hereafter referred to as “initial state”), were characterized by atomic force microscopy (AFM) and size exclusion chromatography (SEC) before behavioral investigation.”
plain- Asserted: passes — The authors put it forward as true.
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Probably 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
“Thus, although Aβ oligomers interact with PrPC with high affinity, they do not act together to induce memory derangement.”
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PrPC has been involved in neurotrophic signaling (44, 45), and in the regulation of Aβ-production (46), suggesting that PrPC and Aβ may be part of a common molecular pathway governing neuronal differentiation.”
What the sources say
- Not checked yetcites [44] Kanaani J, Prusiner SB, Diacovo J, Baekkeskov S, Legname G. Recombinant prion protein induces rapid polarization and development of synapses in embryonic rat hippocampal neurons in vitro. J Neurochem. 2005;95:1373–1386. doi: 10.1111/j.1471-4159.2005.03469.x. [DOI] [PubMed] [Google Scholar]
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plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“However, some human and primate studies have shown that hippocampal lesions result in impaired object recognition (41, 42) and that, for the 24 h intertrial interval from familiarization to test phase used in our study, hippocampal activity is required (43).”
What the sources say
- Not checked yetcites [43] Hammond RS, Tull LE, Stackman RW. On the delay-dependent involvement of the hippocampus in object recognition memory. Neurobiol Learn Mem. 2004;82:26–34. doi: 10.1016/j.nlm.2004.03.005. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably 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
“Memory processing requires NMDA receptor activation and intracellular signaling leading to AMPA receptor trafficking, synthesis of new proteins, and formation of dendritic spines (34, 35).”
What the sources say
- Not checked yetcites [34] Collingridge GL, Isaac JT, Wang YT. Receptor trafficking and synaptic plasticity. Nat Rev Neurosci. 2004;5:952–962. doi: 10.1038/nrn1556. [DOI] [PubMed] [Google Scholar]
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plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The novel-object recognition task is simple and reproducible, it measures recognition memory, which is heavily impaired in AD, and relies on spontaneous animal behavior without the need for stressor elements such as food or water deprivation, electric foot-shock, or aversive environments like water (25).”
What the sources say
- Not checked yetcites [25] Squire LR, Wixted JT, Clark RE. Recognition memory and the medial temporal lobe: A new perspective. Nat Rev Neurosci. 2007;8:872–883. doi: 10.1038/nrn2154. [DOI] [PMC free article] [PubMed] [Google Scholar]
plain- Asserted: passes — The authors put it forward as true.
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Probably 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
“Proof that Aβ oligomers are the active amyloid-β species was the lack of effect of either the freshly solubilized Aβ (initial state) or fibrils.”
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The novel-object recognition task is simple and reproducible, it measures recognition memory, which is heavily impaired in AD, and relies on spontaneous animal behavior without the need for stressor elements such as food or water deprivation, electric foot-shock, or aversive environments like water (25).”
What the sources say
- Not checked yetcites [25] Squire LR, Wixted JT, Clark RE. Recognition memory and the medial temporal lobe: A new perspective. Nat Rev Neurosci. 2007;8:872–883. doi: 10.1038/nrn2154. [DOI] [PMC free article] [PubMed] [Google Scholar]
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“At variance with the native peptide, the depsi-peptide is highly soluble and it has a much lower propensity to aggregate, thus preventing the spontaneous formation of seeds in the solution (49, 50).”
What the sources say
- Not checked yetcites [49] Taniguchi A, et al. “Click peptide”: pH-triggered in situ production and aggregation of monomer Abeta1-42. ChemBioChem. 2009;10:710–715. doi: 10.1002/cbic.200800765. [DOI] [PubMed] [Google Scholar]
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plaindirect- Asserted: passes — The authors put it forward as true.
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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
“One limitation of this study worth to be mentioned may be the use of oligomeric Aβ preparations which haven’t been proven to be identical to those found in the brain of AD patients.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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 novel-object recognition task is simple and reproducible”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
Synthetic Aβ1–42 oligomers injected intracerebroventricularly in mice reproduce the relevant actions of endogenous Aβ oligomers in Alzheimer’s disease.
“These data suggest that Aβ1–42 oligomers are responsible for cognitive impairment in AD and that PrPC is not required.”
“Soluble, bio-derived oligomers of Aβ are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Aβ−mediated cognitive impairment are needed.”
The paper relies on this without support.
There is no consensus as to which brain-derived oligomeric species mediate cognitive deficits in AD.
“since there remains no consensus as to which brain-derived oligomeric species mediate cognitive deficits in AD”
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
“Atomic Force Microscopy (AFM) was used to verify the actual and correct formation of the Aβ1-42 fibrils ([36]) [68,69].”
From PCSK9 affects astrocyte cholesterol metabolism and reduces neuron cholesterol supplying in vitro: potential implications in Alzheimer’s disease (2022) · cites this paper as [69]
In the citing 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)”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Balducci et al., 2010
Citations
Cites
1 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
RetractedMemory - A century of consolidation
McGaugh, J. L. (2000) · Science · doi:10.1126/science.287.5451.248 · Cited by 4,250
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., et al. (2008) · Nature Medicine · doi:10.1038/nm1782 · Cited by 3,685
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506
Mice devoid of PrP are resistant to scrapie
Büeler, H., Aguzzi, A., Sailer, A. W., Greiner, R., Autenried, P., Aguet, M., & Weissmann, C. (1993) · Cell · doi:10.1016/0092-8674(93)90360-3 · Cited by 2,107
Mucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856
Natural oligomers of the amyloid-β protein specifically disrupt cognitive function
Cleary, J. P., Walsh, D. M., Hofmeister, J. J., Shankar, G. M., Kuskowski, M. A., Selkoe, D. J., & Ashe, K. H. (2004) · Nature Neuroscience · doi:10.1038/nn1372 · Cited by 1,722
Shankar, G. M., Bloodgood, B. L., Townsend, M., Walsh, D. M., Selkoe, D. J., & Sabatini, B. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.4970-06.2007 · Cited by 1,592
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 5×
“Almeida CG, et al. (2005) Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses.”
InfluentialCellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2009) · Nature · doi:10.1038/nature07761 · Cited by 1,560
Cited by
Sorted by citations
The Intersection of Amyloid Beta and Tau at Synapses in Alzheimer’s Disease
Spires-Jones, T. L., & Hyman, B. T. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.004 · Cited by 1,201
Neurotoxicity of Amyloid -Protein: Synaptic and Network Dysfunction
Mucke, L., & Selkoe, D. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006338 · Cited by 1,000
The Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s and Fibrillization
Hamley, I. W. (2012) · Chemical Reviews · doi:10.1021/cr3000994 · Cited by 892
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
Busche, M. A., Chen, X., Henning, H. A., Reichwald, J., Staufenbiel, M., Sakmann, B., & Konnerth, A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206171109 · Cited by 715
“In addition, cerebroventricular injections of soluble Aβ rapidly and transiently induce memory deficits in wild-type mice (44), perhaps by causing transient neuronal hyperactivity.”
BackgroundAlzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons
Um, J. W., Nygaard, H. B., Heiss, J. K., Kostylev, M. A., Stagi, M., Vortmeyer, A. O., Wısnıewskı, T., Gunther, E. C., & Strittmatter, S. M. (2012) · Nature Neuroscience · doi:10.1038/nn.3178 · Cited by 682
Amyloid β Protein and Alzheimer’s Disease: When Computer Simulations Complement Experimental Studies
Nasica-Labouze, J., Nguyen, P. H., Sterpone, F., Berthoumieu, O., Buchete, N., Côté, S., Simone, A. D., Doig, A. J., Faller, P., García, A. E., et al. (2015) · Chemical Reviews · doi:10.1021/cr500638n · Cited by 591
Amyloid-Beta: A Crucial Factor in Alzheimer's Disease
Sadigh‐Eteghad, S., Sabermarouf, B., Majdi, A., Talebi, M., Farhoudi, M., & Mahmoudi, J. (2014) · Medical Principles and Practice · doi:10.1159/000369101 · Cited by 563
Alzheimer brain-derived tau oligomers propagate pathology from endogenous tau
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., & Kayed, R. (2012) · Scientific Reports · doi:10.1038/srep00700 · Cited by 502
The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease
Ferreira, S. T., & Klein, W. L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.08.003 · Cited by 442
Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein
Gimbel, D. A., Nygaard, H. B., Coffey, E. E., Gunther, E. C., Laurén, J., Gimbel, Z. A., & Strittmatter, S. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0395-10.2010 · Cited by 418
“Thus, the loss of synaptic marker area caused by APPswe/ PSen1 E9 expression is rescued by a lack of PrPC expression.”
BackgroundInfluentialFerreira, S. T., Lourenco, M. V., Oliveira, M. M., & De Felice, F. G. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00191 · Cited by 373
“…binds AβOs and transduces neurotoxic signals (Laurén et al., 2009), there has been some controversy as to whether PrPC is indeed necessary for oligomer binding and/or oligomer-induced brain dysfunction (Balducci et al., 2010; Kessels et al., 2010; Forloni and Balducci, 2011; Fluharty et al., 2013).”
BackgroundSoluble Aβ oligomer production and toxicity
Larson, M. E., & Lesné, S. E. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07478.x · Cited by 356
“Over the past few years, the prion protein has probably been the most controversial receptor for Ab oligomers (Balducci et al. 2010; Benilova and De Strooper 2010; Calella et al. 2010; Kessels et al. 2010; Barry et al. 2011; Cisse et al. 2011b; Freir et al. 2011).”
BackgroundPrions, prionoids and protein misfolding disorders
Scheckel, C., & Aguzzi, A. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0011-4 · Cited by 311
Alzheimer's disease: synapses gone cold
Koffie, R. M., Hyman, B. T., & Spires‐Jones, T. L. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-63 · Cited by 316
Freir, D. B., Nicoll, A. J., Klyubin, I. V., Panico, S., Donald, J. M. M., Risse, E., Asante, E. A., Farrow, M. A., Sessions, R. B., Saibil, H. R., et al. (2011) · Nature Communications · doi:10.1038/ncomms1341 · Cited by 300
Interaction between Human Prion Protein and Amyloid-β (Aβ) Oligomers
Chen, S., Yadav, S. P., & Surewicz, W. K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.145516 · Cited by 301
Prion-like disorders: blurring the divide between transmissibility and infectivity
Cushman-Nick, M., Johnson, B. S., King, O. D., Gitler, A. D., & Shorter, J. (2010) · Journal of Cell Science · doi:10.1242/jcs.051672 · Cited by 301
“However, it is unclear how the PrP-A oligomer interaction leads to synaptic impairment (Balducci et al., 2010; Lauren et al., 2009).”
BackgroundLarson, M. E., Sherman, M. A., Amar, F., Nuvolone, M., Schneider, J. A., Bennett, D. A., Aguzzi, A., & Lesné, S. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1858-12.2012 · Cited by 290
“Several groups, however, failed to reach the conclusions that A - induced LTP inhibition/cognitive impairment is dependent on PrP c (Balducci et al., 2010; Calella et al., 2010; Kessels et al., 2010), fueling an intense debate regarding the role of PrP c in AD (Benilova and De Strooper, 2010).”
BackgroundResultInfluentialRetractedAlzheimer's disease and type 2 diabetes: a critical assessment of the shared pathological traits
Chatterjee, S., & Mudher, A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00383 · Cited by 270
Li, S., & Selkoe, D. J. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15007 · Cited by 263
“The soluble oAβ binding to PrP was also confirmed in mouse studies (Balducci et al., 2010; Calella et al., 2010; Lauren, Gimbel, Nygaard, Gilbert, & Strittmatter, 2009).”
BackgroundResultThe biological function of the cellular prion protein: an update
Wulf, M.-A., Senatore, A., & Aguzzi, A. (2017) · BMC Biology · doi:10.1186/s12915-017-0375-5 · Cited by 284
“Toxicity elicited by oligomeric species Protected from LTP reduction induced by toxic Aβ species [98] (ZH1, other) [102] (ZH1) [103] (ZH1) [104] (Other) [105] (Other)”
BackgroundModels of β-amyloid induced Tau-pathology: The long and “folded” road to understand the mechanism
Stancu, I.-C., Vasconcelos, B., Terwel, D., & Dewachter, I. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-51 · Cited by 256
“receptor (LilrB2) [77-90].”
Reza-Zaldivar, E. E., Hernández-Sapiéns, M. A., Gutiérrez-Mercado, Y. K., Sandoval-Ávila, S., Gomez-Pinedo, U., Márquez-Aguirre, A. L., Vázquez-Méndez, E., Padilla-Camberos, E., & Canales-Aguirre, A. A. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.255978 · Cited by 256
“These results are similar to those previously reported and are indicative of the proper implementation of the disease model (Nitta et al., 1994; Sipos et al., 2007; Takeda et al., 2009; Balducci et al., 2010; Kim et al., 2016).”
The prion protein as a receptor for amyloid-β
Kessels, H. W., Nguyen, L. N., Nabavi, S., & Malinow, R. (2010) · Nature · doi:10.1038/nature09217 · Cited by 253
Protein phosphorylation in neurodegeneration: friend or foe?
Tenreiro, S., Eckermann, K., & Outeiro, T. F. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00042 · Cited by 252
“Prion protein was proposed as binding partner of Aβ but there is still controversy about the significance of this interaction (Balducci et al., 2010; Kessels et al., 2010; Chen et al., 2013a).”
BackgroundOptogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model
Etter, G., van der Veldt, S., Manseau, F., Zarrinkoub, I., Trillaud-Doppia, É., & Williams, S. (2019) · Nature Communications · doi:10.1038/s41467-019-13260-9 · Cited by 248
“To generate gamma oscillations in PVJ20+ mice, we compared the effects of 10 Hz (theta band), 40 Hz (slow gamma band), and 80 Hz (fast gamma band) optogenetic stimulation and found that 40 Hz stimulation were most effective at increasing slow gamma power in the hippocampus (1ANOVA, F(3, 30)= 6.”
MethodPrion protein and Aβ‐related synaptic toxicity impairment
Calella, A. M., Farinelli, M., Nuvolone, M., Mirante, O., Moos, R., Falsig, J., Mansuy, I. M., & Aguzzi, A. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000082 · Cited by 242
“Firstweverified 2010 EMBO Molecular Medicine that interaction of PrPC with Ab species (Balducci et al, 2010; Lauren et al, 2009) can occur in the absence of PrPC membrane anchoring.”
InfluentialYou, H., Tsutsui, S., Hameed, S., Kannanayakal, T. J., Chen, L., Xia, P., Engbers, J. D. T., Lipton, S. A., Stys, P. K., & Zamponi, G. W. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110789109 · Cited by 254
Barry, A. E., Klyubin, I., Mc Donald, J. M., Mably, A. J., Farrell, M. A., Scott, M., Walsh, D. M., & Rowan, M. J. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.6500-10.2011 · Cited by 237
“However, a rapid A -mediated disruption of object recognition learning was not apparently reduced in Prnp / mice (Balducci et al., 2010), making it important to determine whether cognitive impairment caused by human brain-derived soluble A is dependent on PrP C.”
BackgroundCurcumin-decorated nanoliposomes with very high affinity for amyloid-β1-42 peptide
Mourtas, S., Canovi, M., Zona, C., Aurilia, D., Niarakis, A., Ferla, B. L., Salmona, M., Nicotra, F., Gobbi, M., & Antimisiaris, S. G. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.10.027 · Cited by 234
“TheAb1-42 peptide solution obtained immediately after switching is seed-free as shown in carefully conducted previous work [54,55].”
BackgroundMethodSelf-citationAmyloid-type Protein Aggregation and Prion-like Properties of Amyloids
Willbold, D., Strodel, B., Schroeder, G. F., Hoyer, W., & Heise, H. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00196 · Cited by 226
Rushworth, J. V., & Hooper, N. M. (2010) · International Journal of Alzheimer s Disease · doi:10.4061/2011/603052 · Cited by 234
Lipid-based nanoparticles with high binding affinity for amyloid-β1–42 peptide
Gobbi, M., Re, F., Canovi, M., Beeg, M., Gregori, M., Sesana, S., Sonnino, S., Brogioli, D., Musicanti, C., Gasco, P., et al. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.04.044 · Cited by 192
Self-citationFyn kinase inhibition as a novel therapy for Alzheimer’s disease
Nygaard, H. B., van Dyck, C. H., & Strittmatter, S. M. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt238 · Cited by 206
“PrP is not essential for all Aβ-related phenotypes [36-39].”
BackgroundAlzheimer’s Disease, Oligomers, and Inflammation
Forloni, G., & Balducci, C. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170819 · Cited by 205
Self-citationExosomes neutralize synaptic-plasticity-disrupting activity of Aβ assemblies in vivo
An, K., Klyubin, I. V., Kim, Y., Jung, J. H., Mably, A. J., O’Dowd, S., Lynch, T., Kanmert, D., Lemere, C. A., Finan, G. M., et al. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-47 · Cited by 196
“Multiple independent studies concluded that PrP binds Aβ oligomers specifically and with high affinity [6,7,40,43-45].”
Fluharty, B. R., Biasini, E., Stravalaci, M., Sclip, A., Diomede, L., Balducci, C., Vitola, P. L., Messa, M., Colombo, L., Forloni, G., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.423954 · Cited by 189
“The novel object recognition test was then performed following a previously published protocol (6).”
BackgroundMethodInfluentialSelf-citationMazarati, A. M., Maroso, M., Iori, V., Vezzani, A., & Carli, M. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.08.012 · Cited by 182
“NORT may be used to examine both short term (i.e. familiarization and recognition phases are separated by up to several hours, e.g. Okun et al., 2010) and long-term object memory (specifically at a 24 h interval; Balducci et al., 2010).”
BackgroundMethodResultInfluentialThe intricate mechanisms of neurodegeneration in prion diseases
Soto, C. A., & Satani, N. (2010) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2010.09.001 · Cited by 193
Li, J., Kanekiyo, T., Shinohara, M., Zhang, Y., LaDu, M. J., Xu, H., & Bu, G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.420224 · Cited by 179
Chung, E., Ji, Y., Sun, Y., Kascsak, R. J., Kascsak, R. B., Mehta, P. D., Strittmatter, S. M., & Wisniewski, T. (2010) · BMC Neuroscience · doi:10.1186/1471-2202-11-130 · Cited by 152
“studies also used novel object recognition testing in contrast to radial arm maze or water maze spatial memory testing [9].”
BackgroundMethodPrion protein at the crossroads of physiology and disease
Biasini, E., Turnbaugh, J. A., Unterberger, U., & Harris, D. A. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.10.002 · Cited by 169
Self-citationDecker, H., Jürgensen, S., Adrover, M. F., Brito‐Moreira, J., Bomfim, T. R., Klein, W. L., Epstein, A. L., Felice, F. G. D., Jerusalinsky, D. A., & Ferreira, S. T. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07058.x · Cited by 172
“…other studies have shown that PrP-expressing and PrP-knockout mice are equally susceptible to long-term memory impairment induced by Ab oligomers (Balducci et al. 2010; Calella et al. 2010), supporting the notion that, at least in part, the deleterious effects of Ab oligomers on plasticity are…”
BackgroundFalker‐Gieske, C., Hartmann, A., Guett, I., Dohler, F., Altmeppen, H. C., Betzel, C., Schubert, R., Thurm, D., Wegwitz, F., Joshi, P., et al. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13514 · Cited by 166
“If and how this binding affects synaptotoxicity is a matter of debate (Balducci et al. 2010; Calella et al. 2010; Kessels et al. 2010; Cisse et al. 2011) [reviewed in Benilova and De Strooper (2010)].”
BackgroundNygaard, H. B., Wagner, A. F., Bowen, G. S., Good, S. P., MacAvoy, M. G., Strittmatter, K. A., Kaufman, A. C., Rosenberg, B. J., Sekine-Konno, T., Varma, P., et al. (2015) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0119-0 · Cited by 168
“Aβ binding to PrP is highly conformation-dependent, and only Aβo will interact with PrP , with no binding detected in the presence of fibrillary or monomeric Aβ peptide [5,7-9].”
BackgroundBalducci, C., Frasca, A., Zotti, M., La Vitola, P., Mhillaj, E., Grigoli, E., Iacobellis, M., Grandi, F., Messa, M., Colombo, L., et al. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.10.012 · Cited by 164
“Scheme 1 summarizes the treatment schedules for NORT experiments 2.5 Object recognition task.”
BackgroundMethodInfluentialSelf-citationBalducci, C., Mancini, S., Minniti, S., La Vitola, P., Zotti, M., Sancini, G., Mauri, M., Cagnotto, A., Colombo, L., Fiordaliso, F., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0284-14.2014 · Cited by 162
“In experimental models, oligomers have been shown to specifically inhibit long-term potentiation and mediate memory impairment, whereas A monomer and fibrils were inactive (Walsh et al., 2002; Cleary et al., 2005; Balducci et al., 2010).”
BackgroundSelf-citationTaylor, M., Moore, S., Mayes, J., Parkin, E. T., Beeg, M., Canovi, M., Gobbi, M., Mann, D. M. A., & Allsop, D. (2010) · Biochemistry · doi:10.1021/bi100144m · Cited by 166
Self-citationCorbett, G. T., Wang, Z., Hong, W., Colom‐Cadena, M., Rose, J. L., Liao, M., Asfaw, A., Hall, T. C., Ding, L., DeSousa, A., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02114-9 · Cited by 161
Protein aggregation: Mechanisms and functional consequences
Invernizzi, G., Papaleo, E., Sabaté, R., & Ventura, S. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.05.023 · Cited by 165
Aβ Oligomer-Induced Synapse Degeneration in Alzheimer’s Disease
Wilcox, K. C., Lacor, P. N., Pitt, J. E., & Klein, W. L. (2011) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-011-9691-4 · Cited by 159
“The prospect that PrPc is the binding site for Ab oligomers was quickly and alternately refuted (Calella et al. 2010; Kessels et al. 2010; Balducci et al. 2010) and supported (Gimbel et al. 2010; Chen et al. 2010) by multiple follow-up studies.”
Rushworth, J. V., Jarosz-Griffiths, H., Watt, N. T., & Hooper, N. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.400358 · Cited by 157
“Although the binding of A oligomers to PrP has been confirmed by several groups (14, 18–21), whether PrP mediates the downstream A oligomer neurotoxicity remains controversial (19, 20, 22).”
BackgroundVitamin A and Alzheimer's disease
Ono, K., & Yamada, M. (2011) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2011.00786.x · Cited by 156
The immunobiology of prion diseases
Aguzzi, A., Nuvolone, M., & Zhu, C. (2013) · Nature reviews. Immunology · doi:10.1038/nri3553 · Cited by 150
Cell Biology of Prions and Prionoids: A Status Report
Aguzzi, A., & Lakkaraju, A. K. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.08.007 · Cited by 148
Haas, L. T., Salazar, S. V., Kostylev, M. A., Um, J. W., Kaufman, A. C., & Strittmatter, S. M. (2015) · Brain · doi:10.1093/brain/awv356 · Cited by 145
“Amyloid-b oligomers bind to PrP with high affinity (Lauren et al., 2009; Balducci et al., 2010; Zou et al., 2011) and multiple studies support a role for PrP in mediating Alzheimer’s disease-related pathology (Lauren et al.”
BackgroundXia, N., Wang, X., Zhou, B., Wu, Y., Mao, W., & Liu, L. (2016) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.6b05423 · Cited by 145
The Biological Function of the Prion Protein: A Cell Surface Scaffold of Signaling Modules
Linden, R. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00077 · Cited by 151
“Notably, however, the reputed role of the prion protein as a receptor for AßO is not exclusive (Balducci et al., 2010; Calella et al., 2010; Cissé et al., 2011; Forloni and Balducci, 2011).”
BackgroundTREM2 promotes Aβ phagocytosis by upregulating C/EBPα-dependent CD36 expression in microglia
Kim, S.-M., Mun, B.-R., Lee, S.-J., Joh, Y., Lee, H.-Y., Ji, K.-Y., Choi, H.-R., Lee, E.-H., Kim, E.-M., Jang, J.-H., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11634-x · Cited by 143
Biosensors for Alzheimer's disease biomarker detection: A review
Shui, B., Tao, D., Florea, A., Cheng, J., Zhao, Q., Gu, Y., Li, W., Jaffrezic-Renault, N. J., Mei, Y., & Guo, Z. (2018) · Biochimie · doi:10.1016/j.biochi.2017.12.015 · Cited by 139
Cortical hypermetabolism in MCI subjects: a compensatory mechanism?
Ashraf, A., Fan, Z., Brooks, D. J., & Edison, P. (2014) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-014-2919-z · Cited by 143
“More convincingly, cerebroventricular injections of soluble Aβ induced rapid and transient memory deficits in wild-type mice [33, 34].”
BackgroundKostylev, M. A., Kaufman, A. C., Nygaard, H. B., Patel, P., Haas, L. T., Gunther, E. C., Vortmeyer, A., & Strittmatter, S. M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.643577 · Cited by 133
“However, some studies provide evidence for PrP-independent A o-induced phenotypes, thus conflicting with the data supporting the role of PrP-A o interaction in AD (23, 24, 44, 45).”
BackgroundResultEvangelisti, E., Cascella, R., Becatti, M., Marrazza, G., Dobson, C. M., Chiti, F., Stefani, M., & Cecchi, C. (2016) · Scientific Reports · doi:10.1038/srep32721 · Cited by 133
Wilkaniec, A., Gąssowska-Dobrowolska, M., Strawski, M., Adamczyk, A., & Czapski, G. A. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-017-1027-y · Cited by 133
“motion and exploration were observed [42, 78].”
Switchable photooxygenation catalysts that sense higher-order amyloid structures
Taniguchi, A., Shimizu, Y., Oisaki, K., Sohma, Y., & Kanai, M. (2016) · Nature Chemistry · doi:10.1038/nchem.2550 · Cited by 129
FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer’s disease
Kam, T.-I., Song, S., Gwon, Y., Park, H., Yan, J.-J., Im, I., Choi, J.-W., Choi, T.-Y., Kim, J., Song, D.-K., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66827 · Cited by 128
“Many studies have used synthetic Aβ1-42 to induce neuronal death in vitro (9, 28, 29).”
Beeg, M., Stravalaci, M., Romeo, M., Carrà, A. D., Cagnotto, A., Rossi, A., Diomede, L., Salmona, M., & Gobbi, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.689539 · Cited by 128
“However, it was not possible to use this binding signal to correct that observed in the presence of oligomers, i.e. to obtain the oligomer-dependent signal, because the resulting sensorgrams had unusual shapes (i.e. increase of SPR signal during the dissociation phase).”
MethodInfluentialSelf-citationGomes, L. A., Hipp, S. A., Rijal Upadhaya, A., Balakrishnan, K., Ospitalieri, S., Koper, M. J., Largo-Barrientos, P., Uytterhoeven, V., Reichwald, J., Rabe, S., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02053-5 · Cited by 125
Prion propagation, toxicity and degradation
Aguzzi, A., & Falsig, J. (2012) · Nature Neuroscience · doi:10.1038/nn.3120 · Cited by 126
Heraldo, F. H., Arantes, C., Santos, T. G., Machado, C. F., Roffé, M., Haji, G. N., Lee, K. S., Magalhães, A. C., Caetano, F. A., Mancini, G. L., et al. (2010) · The FASEB Journal · doi:10.1096/fj.10-161653 · Cited by 123
Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity
Nicoll, A. J., Panico, S., Freir, D. B., Wright, D., Terry, C., Risse, E., Herron, C. E., O’Malley, T., Wadsworth, J. D. F., Farrow, M. A., et al. (2013) · Nature Communications · doi:10.1038/ncomms3416 · Cited by 119
Cissé, M., Sanchez, P. E., Kim, D. H., Ho, K., Yu, G.-Q., & Mucke, L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.1459-11.2011 · Cited by 124
“Because A binds to many molecules (Dineley et al., 2002; Laurén et al., 2009; Origlia et al., 2009; Balducci et al., 2010; Renner et al., 2010; Cissé et al., 2011), it is critical to determine which of these interactions have the greatest functional impact.”
BackgroundInfluentialThe case for soluble Aβ oligomers as a drug target in Alzheimer's disease
Hefti, F. F., Goure, W. F., Jerecìć, J., Iverson, K. S., Walicke, P. A., & Krafft, G. A. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.03.002 · Cited by 122
Rezabakhsh, A., Rahbarghazi, R., & Fathi, F. (2020) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2020.112511 · Cited by 120
The dendritic hypothesis for Alzheimer's disease pathophysiology
Cochran, J. N., Hall, A. M., & Roberson, E. D. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.12.004 · Cited by 114
“However, in other studies these effects of blocking PrP were not replicated, including effects on LTP [29, 108] and behavior [14, 39].”
BackgroundNoncanonical function of an autophagy protein prevents spontaneous Alzheimer’s disease
Heckmann, B. L., Teubner, B. J. W., Boada-Romero, E., Tummers, B., Guy, C., Fitzgerald, P., Mayer, U., Carding, S., Zakharenko, S. S., Wileman, T., et al. (2020) · Science Advances · doi:10.1126/sciadv.abb9036 · Cited by 114
Xia, N., Zhou, B., Huang, N., Jiang, M., Zhang, J., & Liu, L. (2016) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2016.05.066 · Cited by 119
The keystone of Alzheimer pathogenesis might be sought in Aβ physiology
Puzzo, D., Gulisano, W., Arancio, O., & Palmeri, A. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.08.039 · Cited by 116
“…Vitolo et al., 2002; Walsh et al., 2002; Cleary et al., 2005; Puzzo et al., 2005; Townsend et al., 2006; Shankar et al., 2007, 2008; Selkoe, 2008; Balducci et al., 2010); (iii) APP transgenic mice present the cognitive impairment before amyloid deposition (Chapman et al., 1999; Hsia et al.,…”
Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease
Um, J. W., & Strittmatter, S. M. (2013) · Prion · doi:10.4161/pri.22212 · Cited by 115
Cellular prion protein is essential for oligomeric amyloid- -induced neuronal cell death
Kudo, W., Hp, L., Zou, W.-Q., Wang, X., Perry, G., Zhu, X., Smith, M. A., Petersen, R. B., & Lee, H. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr542 · Cited by 116
Oligomeropathies and pathogenesis of Alzheimer and Parkinson's diseases
Forloni, G., Artuso, V., Vitola, P. L., & Balducci, C. (2016) · Movement Disorders · doi:10.1002/mds.26624 · Cited by 116
Self-citationIntranasal delivery of mesenchymal stem cell secretome repairs the brain of Alzheimer’s mice
Santamaria, G., Brandi, E., Vitola, P. L., Grandi, F., Ferrara, G. B., Pischiutta, F., Vegliante, G., Zanier, E. R., Re, F., Uccelli, A., et al. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-0592-2 · Cited by 124
Self-citationLee, Y. W., Kim, D. H., Jeon, S. J., Park, S. J., Kim, J. M., Jung, J. M., Lee, H. E., Bae, S. G., Oh, H. K., Son, K. H., et al. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.02.015 · Cited by 114
“Several factors are known to cause Alzheimer’s disease, such as neurofibrillary tangles related to hyper-phosphorylated tau proteins (Iqbal et al., 2010) and senile plaques composed of amyloid b (Ab) protein (Balducci et al., 2010; Nabeshima and Nitta, 1994; Vickers et al., 2000).”
BackgroundNeuropathogenesis-on-chips for neurodegenerative diseases
Amartumur, S., Nguyen, H. M., Huynh, T., Kim, T. S., Woo, R., Oh, E., Kim, K. K., Lee, L. P., & Heo, C. (2024) · Nature Communications · doi:10.1038/s41467-024-46554-8 · Cited by 131
“Numerous studies have used exogenous recombinant human and mouse proteins to characterise misfolded protein pathologies both in vitro 362 and in vivo 426 . α -syn preformed fi brils generated from monomeric recombinant α -syn can induce hyperphosphorylation of endogenous α -syn and enhance the…”
BackgroundThe Essential Role of Soluble Aβ Oligomers in Alzheimer’s Disease
Wang, Z.-X., Tan, L., Liu, J., & Yu, J.-T. (2016) · Molecular Neurobiology · doi:10.1007/s12035-015-9143-0 · Cited by 110
Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity
Smith, L. M., & Strittmatter, S. M. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024075 · Cited by 109
Shibuya, Y., Chang, C. C. Y., Huang, L.-H., Bryleva, E. Y., & Chang, T.-Y. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2567-14.2014 · Cited by 108
“For instance, intracerebroventricular injections of synthetic A 1– 42 oligomers, but not A 1– 42 fibrils, impair long-term memory in mice (Balducci et al., 2010).”
BackgroundAlpha Synuclein: Neurodegeneration and Inflammation
Forloni, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065914 · Cited by 116
Self-citationWhitcomb, D. J., Hogg, E. L., Regan, P. L., Piers, T. M., Narayan, P. S., Whitehead, G., Winters, B. L., Kim, D.-H., Kim, E., George‐Hyslop, P. S., et al. (2015) · Scientific Reports · doi:10.1038/srep10934 · Cited by 108
Fišar, Z. (2022) · Biomolecules · doi:10.3390/biom12111676 · Cited by 113
Astrocytes in Alzheimer's Disease: Emerging Roles in Calcium Dysregulation and Synaptic Plasticity
Vincent, A. J., Gasperini, R., Foa, L. C., & Small, D. H. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-101089 · Cited by 106
“humans [21–25,166].”
InfluentialAlzheimer’s Disease: Mechanism and Approach to Cell Therapy
Amemori, T., Jendelová, P., Růžička, J., Urdzíková, L. M., & Syková, E. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161125961 · Cited by 110
“Ablation or overexpression of PrPC had no effect on hippocampal synaptic plasticity and oligomer-induced cognitive impairment [137,138].”
BackgroundHigaki, S., Muramatsu, M., Matsuda, A., Matsumoto, K., Satoh, J., Michikawa, M., & Niida, S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0196929 · Cited by 103
Younan, N. D., Sarell, C. J., Davies, P., Brown, D. R., & Viles, J. H. (2013) · The FASEB Journal · doi:10.1096/fj.12-222588 · Cited by 104
Alzheimer’s disease Aβ assemblies mediating rapid disruption of synaptic plasticity and memory
Klyubin, I. V., Cullen, W. K., Hu, N., & Rowan, M. J. (2012) · Molecular Brain · doi:10.1186/1756-6606-5-25 · Cited by 105
“However, an apparent acute disruption of object recognition memory caused by Aβ1-42 was not prevented in mice lacking PrP [117].”
BackgroundCronican, A. A., Fitz, N. F., Carter, A., Saleem, M., Shiva, S., Barchowsky, A., Koldamova, R. P., Schug, J., & Lefterov, I. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053478 · Cited by 102
“Following testing in the RWM changes in long term memory was assessed utilizing a novel object recognition behavioral paradigm [22,23].”
MethodTargeting Synaptic Dysfunction in Alzheimer’s Disease Therapy
Nisticò, R., Pignatelli, M., Piccinin, S., Mercuri, N. B., & Collingridge, G. L. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8324-3 · Cited by 102
“While these findings indicate the potential usefulness of immunotherapeutically targeting the binding of synaptotoxic Aβ assemblies to PrPC, two studies [60, 61] and experiments performed in our laboratory (unpublished data) have generated conflicting results.”
Dinamarca, M. C., Ríos, J. A., & Inestrosa, N. C. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00464 · Cited by 105
“However, other reports questioned these findings because the absence of PrPc did not prevent Aβ oligomer-mediated synaptic toxicity or cognitive impairment (Balducci et al., 2010; Calella et al., 2010; Kessels et al., 2010).”
ResultThe function of the cellular prion protein in health and disease
Watts, J. C., Bourkas, M. E. C., & Arshad, H. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1790-y · Cited by 105
Metadata
- Authors
- Balducci, C., Beeg, M., Stravalaci, M., Bastone, A., Sclip, A., Biasini, E., Tapella, L., Colombo, L., Manzoni, C., Borsello, T., Chiesa, R., Gobbi, M., Salmona, M., & Forloni, G.
- Affiliations
- Mario Negri Institute for Pharmacological Research (IT)
- Dulbecco Telethon Institute (IT)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-01-19
- Volume
- 107
- Issue
- 5
- Pages
- 2295-2300
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2836680
- OpenAlex
- W2002280328
- Semantic Scholar
- 63625a2fc958c65a2cb276db617f403efa9be515
- Cited by
- 466
- References
- 57
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 14 · 2023: 19 · 2022: 20 · 2021: 24 · 2020: 31 · 2019: 25 · 2018: 32 · 2017: 40 · 2016: 31 · 2015: 35 · 2014: 27 · 2013: 47 · 2012: 36
- FWCI
- 33.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Iris (University of Trento) (submittedVersion)
- 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
- amyloid-beta oligomers, amyloid-beta 42, Alzheimer's disease, long-term memory, memory consolidation, recognition memory, cellular prion protein, anti-amyloid antibodies, cognitive impairment, intracerebroventricular administration, amyloid fibrils
- MeSH terms
- Prion Proteins, Alzheimer Disease, Animals, Cognition Disorders, Humans, Injections, Intraventricular, Male, Memory, Mice, Inbred C57BL, Neuronal Plasticity, Peptide Fragments, Prions, Protein Binding, Amyloid beta-Peptides, Mice, Knockout, PrPC Proteins, Surface Plasmon Resonance, Mice
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