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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
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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
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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
Items 301–400 of 468
Unraveling the Vicious Cycle: Oxidative Stress and Neurotoxicity in Neurodegenerative Diseases
Wang, X., Dong, B., Gan, Q., Li, J., Wu, P., Guan, Y., & Wang, J. (2025) · FASEB BioAdvances · doi:10.1096/fba.2025-00093 · Cited by 24
Overcoming barriers and thresholds – signaling of oligomeric Aβ through the prion protein to Fyn
Wang, H., Ren, C. H., Gunawardana, C. G., & Schmitt‐Ulms, G. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-24 · Cited by 18
“However, an ongoing controversy surrounds the significance of oAβ binding to PrP and, more specifically, the question whether this interaction is responsible for downstream neurotoxicity and impairment of long-term potentiation [12,16,17], an electrophysiological surrogate of learning and memory formation.”
BackgroundRescuing neurons in prion disease
Verity, N., & Mallucci, G. R. (2010) · Biochemical Journal · doi:10.1042/bj20101323 · Cited by 19
Medicinal Chemistry Focusing on Aggregation of Amyloid-β
Sohma, Y. (2015) · Chemical and Pharmaceutical Bulletin · doi:10.1248/cpb.c15-00742 · Cited by 19
Effects of Prion Protein on Aβ42 and Pyroglutamate-Modified AβpΕ3-42 Oligomerization and Toxicity
Pagano, K., Galante, D., D’Arrigo, C., Corsaro, A., Nizzari, M., Florio, T., Molinari, H., Tomaselli, S., & Ragona, L. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1202-x · Cited by 20
Microglia CREB-Phosphorylation Mediates Amyloid-β-Induced Neuronal Toxicity
Gao, Y., Liu, E.-J., Wang, W.-J., Wang, Y., Li, X., Wang, X., Li, S., Zhang, S., Li, M., Zhou, Q., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180286 · Cited by 18
Kong, C., Xie, H., Gao, Z., Shao, M., Li, H., Shi, R., Cai, L., Gao, S., Sun, T., & Li, C. (2019) · Virologica Sinica · doi:10.1007/s12250-019-00124-1 · Cited by 18
Comparison of Tau and Amyloid-β Targeted Immunotherapy Nanoparticles for Alzheimer’s Disease
Mashal, Y., Abdelhady, H. G., & Iyer, A. K. (2022) · Biomolecules · doi:10.3390/biom12071001 · Cited by 21
“of oligomeric Aβ in mice and in vitro in hippocampal slice cultures [18].”
BackgroundInfluentialPrion protein expression alters APP cleavage without interaction with BACE-1
McHugh, P., Wright, J. A., Williams, R. J., & Brown, D. R. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.07.002 · Cited by 18
Honda, R. P. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201800197 · Cited by 18
Recent developments in the chemical biology of amyloid-β oligomer targeting
Wang, Y., Chen, J., Gao, F., Hu, M., & Wang, X. (2023) · Organic & Biomolecular Chemistry · doi:10.1039/d3ob00509g · Cited by 20
The Heart of the Alzheimer's: A Mindful View of Heart Disease
Evangelisti, A., Butler, H. M., & del Monte, F. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.625974 · Cited by 17
“PAO and other pre-amyloidogenic species have been found to correlate with disease severity independently of amyloid fibril formation (Balducci et al., 2010; Currais et al., 2016; Chen and Mobley, 2019).”
BackgroundAnastasio, T. J. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00085 · Cited by 17
“Although A β oligomers bind prion protein, such binding is not involved in A β effects on memory (Balducci et al., 2010).”
BackgroundTau oligomers impair memory and synaptic plasticity through the cellular prion protein
Balducci, C., Orsini, F., Cerovic, M., Beeg, M., Rocutto, B., Dacomo, L., Masone, A., Busani, E., Raimondi, I., Lavigna, G., et al. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-01930-3 · Cited by 16
Self-citationNicastro, L. K., de Anda, J., Jain, N., Grando, K. C. M., Miller, A. L., Bessho, S., Gallucci, S., Wong, G. C. L., & Tükel, Ç. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010742 · Cited by 18
Jain, U., Johari, S., & Srivastava, P. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03671-7 · Cited by 16
“Beta and gamma secretases, which work against this, cleave APP in a direction toward the left, releasing two important proteins called the amyloid intracellular domain (AICD) and amyloid-like protein (ALP) [34, 35].”
Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP
Sakudo, A., & Onodera, T. (2015) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2014.00075 · Cited by 16
“…Aβ, although the use of different in vitro or transgenic models has yielded contrasting results (Schwarze-Eicker et al., 2005; Laurén et al., 2009; Balducci et al., 2010; Calella et al., 2010; Chung et al., 2010; Kessels et al., 2010; Morales et al., 2010; Ordóñez-Gutiérrez et al., 2013;…”
ResultThe Anti-Prion Antibody 15B3 Detects Toxic Amyloid-β Oligomers
Stravalaci, M., Tapella, L., Beeg, M., Rossi, A., Joshi, P., Pizzi, E., Mazzanti, M., Balducci, C., Forloni, G., Biasini, E., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150882 · Cited by 15
“A 42 oligomers bound rmPrP immobilized on the sensor chip with high affinity, confirming previous results [5, 20] (Fig.”
BackgroundResultInfluentialSelf-citationRepositioning doxycycline for treating synucleinopathies: Evidence from a pre-clinical mouse model
Vitola, P. L., Artioli, L., Cerovic, M., Poletto, C., Dacomo, L., Leva, S., Balducci, C., & Forloni, G. (2022) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2022.105229 · Cited by 17
Self-citationLiu, J. Y. H., Sun, M. Y. Y., Sommerville, N. R., Ngan, M. P., Ponomarev, E. D., Lin, G., & Rudd, J. A. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111396 · Cited by 15
Noncanonical regulation of imprinted gene Igf2 by amyloid-beta 1–42 in Alzheimer’s disease
Fertan, E., Gendron, W. A. C., Wong, A. A., Hanson, G. M., Brown, R. E., & Weaver, I. C. G. (2023) · Scientific Reports · doi:10.1038/s41598-023-29248-x · Cited by 15
Lewis, V., Whitehouse, I. J., Baybutt, H. N., Manson, J. C., Collins, S. J., & Hooper, N. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031754 · Cited by 15
“Some results suggest that Ab oligomer synaptic toxicity is mediated through its binding to PrP [7,11,12], whereas others have reported that Ab oligomer neurotoxicity is independent of PrP expression [8,9].”
BackgroundYoshiya, T., Higa, A., Abe, N., Fukao, F., Kuruma, T., Toda, Y., Sohma, Y., & Kiso, Y. (2011) · ChemBioChem · doi:10.1002/cbic.201100025 · Cited by 15
Tapella, L., Stravalaci, M., Bastone, A., Biasini, E., Gobbi, M., & Chiesa, R. (2013) · Biochemical Journal · doi:10.1042/bj20130563 · Cited by 15
Self-citationCorreia, A. D. S., Schmitz, M., Fischer, A., Correia, S., Simonetti, F. L., Saher, G., Goya‐Maldonado, R., Arora, A. S., Fischer, A., Outeiro, T. F., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14120 · Cited by 13
“One study found colocalization of PrP C and Cav-1, along with an interaction between PrP C ’s octa repeat region and Cav-1.”
Soluble Aβ aggregates can inhibit prion propagation
Sarell, C. J., Quarterman, E., Yip, D. C.-M., Terry, C., Nicoll, A. J., Wadsworth, J. D. F., Farrow, M. A., Walsh, D. M., & Collinge, J. (2017) · Open Biology · doi:10.1098/rsob.170158 · Cited by 14
Association of prion protein with cognitive functioning in humans
Breitling, L. P., Müller, H., Stegmaier, C., Kliegel, M., & Brenner, H. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.08.001 · Cited by 14
“In the meantime, the PrP c mechanism in Alzheimer's disease has been questioned by some investigators (Balducci et al., 2010; Kessels et al., 2010), but supported by others Bate and Williams (2011), who suggested differences in amyloid-β preparations and memory assessments as possible explanations…”
Aβ dimers induce behavioral and neurochemical deficits of relevance to early Alzheimer's disease
Abdel‐Hafiz, L., Müller‐Schiffmann, A., Korth, C., Fazari, B., Chao, O. Y.-H., Nikolaus, S., Schäble, S., Herring, A., Keyvani, K., Lamounier‐Zepter, V., et al. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.04.005 · Cited by 13
Dexter, E., & Kong, Q. (2021) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2021.1965881 · Cited by 14
A mix-and-click method to measure amyloid-β concentration with sub-micromolar sensitivity
Xue, C., Lee, Y. K., Tran, J., Chang, D., & Guo, Z. (2017) · Royal Society Open Science · doi:10.1098/rsos.170325 · Cited by 13
A Network-Guided Reaction-Diffusion Model of AT[N] Biomarkers in Alzheimer’s Disease
Zhang, J., Yang, D., He, W., Guorong Wu, A., & Chen, M. (2020) · IEEE International Conference on Bioinformatics and Bioengineering (BIBE) · doi:10.1109/bibe50027.2020.00044 · Cited by 13
“Recently, growing evidence in culture models and animal models favors the oligomeric amyloid hypothesis and suggests oligomeric amyloid as a central pathogenic role in AD progression [14], [15].”
BackgroundTherapeutic Potential of Nanomedicine in Management of Alzheimer’s Disease and Glioma
Anwar, F., Al-Abbasi, F. A., Naqvi, S., Sheikh, R. A., Alhayyani, S., Asseri, A. H., Asar, T. O., & Kumar, V. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s405454 · Cited by 15
“Progressive and spontaneous aggregation of Aβ forming oligomers and fibrils with final deposition of senile plaques are the main products responsible for memory deficit and synaptic damage in AD patients.(11,12) Along with Aβ proteins, metabolomics, proteomics and genomic studies have identified various markers that c…”
BackgroundTimofeeva, A. M., Aulova, K. S., & Nevinsky, G. A. (2025) · Brain Sciences · doi:10.3390/brainsci15050486 · Cited by 17
“Low-molecular-weight oligomeric prefibrillar A β aggregates have been shown to be the most cytotoxic forms [223], impair long-term memory after injection into mice [224–226], impair synaptic plasticity, and cause cognitive impairment in rats [227].”
The P’s and Q’s of cellular PrP-Aβ interactions
Westaway, D. A., & Jhamandas, J. H. (2012) · Prion · doi:10.4161/pri.20675 · Cited by 13
The neurodegeneration in Alzheimer disease and the prion protein
Forloni, G., Sclip, A., Borsello, T., & Balducci, C. (2013) · Prion · doi:10.4161/pri.23286 · Cited by 13
Self-citationPrion diseases: New considerations
Annus, Á., Csáti, A., & Vécsei, L. (2016) · Clinical Neurology and Neurosurgery · doi:10.1016/j.clineuro.2016.09.006 · Cited by 13
Scialò, C., & Legname, G. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.08.008 · Cited by 12
Stimmell, A. C., Xu, Z., Moseley, S. C., Cushing, S. D., Fernández, D. M. V., Dang, J. V., Santos-Molina, L. F., Anzalone, R. A., Garcia-Barbon, C. L., Rodriguez, S., et al. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.655015 · Cited by 11
“It is possible that impaired formation of new proteins and dendritic spines may be leading to alterations in neural function, since these processes are important in memory and have been shown to be affected by Aβ (Balducci et al., 2010; Sadigh-Eteghad et al., 2015; Baglietto-Vargas et al., 2018).”
BackgroundChang, Y. K., Xia, N., Huang, Y., et al. (2021) · Nanomaterials · doi:10.3390/nano11123307 · Cited by 12
Cellular prion protein and Alzheimer disease
Kudo, W., Petersen, R. B., & Lee, H. (2013) · Prion · doi:10.4161/pri.22848 · Cited by 12
“However, three independent studies failed to confirm that PrP played a critical role either in vivo or in vitro.(4-6) Balducci et al.”
BackgroundMegra, B., Eugenin, E., Roberts, T. K., Morgello, S., & Berman, J. W. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9458-4 · Cited by 12
“…reported that PrP c did not have a role in Aβ oligomers synaptoxocity and that the absence of PrP c did not prevent the blocking of long term potentiation (Balducci et al. 2010; Calella et al. 2010; Kessels et al. 2010), and learning and memory deficits (Cissé et al. 2011) caused by Aβ oligomers.”
Targeting The Cellular Prion Protein To Treat Neurodegeneration
Biasini, E., & Harris, D. A. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.114 · Cited by 12
Self-citationFunction of Prion Protein and the Family Member, Shadoo
Onodera, T., Nishimura, T., Sugiura, K., & Sakudo, A. (2019) · Current Issues in Molecular Biology · doi:10.21775/cimb.036.067 · Cited by 12
Iraci, N., Stincardini, C., Barreca, M. L., & Biasini, E. (2014) · Virus Research · doi:10.1016/j.virusres.2014.10.015 · Cited by 12
Self-citationQin, K., Zhao, L., Gregory, C., Solanki, A., & Mastrianni, J. A. (2019) · Scientific Reports · doi:10.1038/s41598-019-44317-w · Cited by 12
Whitechurch, B. C., Welton, J. M., Collins, S. J., & Lawson, V. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-57193-5_13 · Cited by 15
Synthesis of O ‐Acyl Isopeptides
Sohma, Y., & Kiso, Y. (2013) · The Chemical Record · doi:10.1002/tcr.201200023 · Cited by 11
Key Alzheimer's findings questioned
Ledford, H. K. (2010) · Nature · doi:10.1038/4661031a · Cited by 11
Béland, M., & Roucou, X. (2013) · Prion · doi:10.4161/pri.27438 · Cited by 12
A common pathway for detergent-assisted oligomerization of Aβ42
Muhammedkutty, F. N. K., Prasad, R., Gao, Y., Sudarshan, T. R., Robang, A. S., Watzlawik, J. O., Rosenberry, T. L., Paravastu, A. K., & Zhou, H. (2023) · Communications Biology · doi:10.1038/s42003-023-05556-w · Cited by 10
Electrochemical Methods for Detecting β-Amyloid Peptides and Monitoring Their Aggregation
Liu, L., & Zhou, B. (2015) · International Journal of Electrochemical Science · doi:10.1016/s1452-3981(23)17381-0 · Cited by 10
Lavigna, G., Masone, A., Bouybayoune, I., Bertani, I., Lucchetti, J., Gobbi, M., Porcu, L., Zordan, S., Rigamonti, M., Imeri, L., et al. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105455 · Cited by 10
Self-citationRole of amyloid β protein receptors in mediating synaptic plasticity
Li, Y., Sun, Z., Cao, Q., Chen, M., Luo, H., Lin, X., & Xiao, F. (2017) · Biomedical Reports · doi:10.3892/br.2017.863 · Cited by 11
Brain region-specific myelinogenesis is not directly linked to amyloid-β in APP/PS1 transgenic mice
Wu, S.-L., Yu, B., Cheng, Y.-J., Ren, S.-Y., Wang, F., Xiao, L., Chen, J., & Mei, F. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114344 · Cited by 9
Beeg, M., Battocchio, E., Luigi, A. D., Colombo, L., Natale, C., Cagnotto, A., Corbelli, A., Fiordaliso, F., Diomede, L., Salmona, M., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100664 · Cited by 9
“Previous studies showed that toxic high–molecular-weight aggregates are formed during the incubation of highly concentrated Aβ1–42 solutions (13, 18).”
BackgroundSelf-citationQu, X., Lin, L., Yi, W., Sun, C., Chen, Y., & Chen, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23168888 · Cited by 9
Lacham‐Hartman, S., Moshe, R., Ben-Zichri, S., Shmidov, Y., Bitton, R., Jelinek, R., & Papo, N. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00208 · Cited by 8
Time-Resolved Observation of Evolution of Amyloid-β Oligomer with Temporary Salt Crystals
Nakajima, K., Yamazaki, T., Kimura, Y., et al. (2020) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.0c01487 · Cited by 9
“9,10 While neurotoxicity of amyloid fibrils has been indicated, 11,12 oligomeric disordered aggregates are also recognized as toxic materials; some recent studies 13,14 insist that their neurotoxicity is greater than that of fibrils.”
Sleep inhibition induced by amyloid‐β oligomers is mediated by the cellular prion protein
Gallo, F. D., Bianchi, S., Bertani, I., Messa, M., Colombo, L., Balducci, C., Salmona, M., Imeri, L., & Chiesa, R. (2020) · Journal of Sleep Research · doi:10.1111/jsr.13187 · Cited by 10
“Because soluble Aβ oligomers are the key mediators of synaptic and cognitive dysfunction in AD (Mucke & Selkoe, 2012) and impair long-term memory in rodents (Balducci et al., 2010), the first aim of this study was to test the hypothesis that such oligomers directly impair sleep in mice.”
BackgroundSelf-citationEffects of External Beam Radiation onIn VitroFormation of Abeta1-42 Fibrils and Preformed Fibrils
Patrias, L. M., Klaver, A. C., Coffey, M. P., Finke, J. M., Digambaranath, J. L., Dang, L., Martinez, A. A., & Loeffler, D. A. (2011) · Radiation Research · doi:10.1667/rr2448.1 · Cited by 9
Sohma, Y., Wang, H., Taniguchi, A., Hirayama, Y., Kakizawa, T., Yamasaki, M., Mukai, H., & Kiso, Y. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.04.056 · Cited by 9
Conceição, M., Filippo, L. D. D., Duarte, J. L., Beserra, F. P., Gremião, M. P. D., & Chorilli, M. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100894 · Cited by 8
Amini, N., Azad, R. R., Motamedi, F., Mirzapourdelavar, H., Ghasemi, S., Aliakbari, S., & Pourbadie, H. G. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.11.001 · Cited by 8
Myers, R. R., Sanchez-Garcia, J., Levings, D. C., Melvin, R. G., & Fernández-Fúnez, P. (2022) · Disease Models & Mechanisms · doi:10.1242/dmm.049184 · Cited by 8
“…et al., 2010; Balducci et al., 2010), this interaction was confirmed by using different techniques, although studies still disagree on the functional meaning of this interaction (Chen et al., 2010; Zou et al., 2011; Gimbel et al., 2010; Gunther and Strittmatter, 2010; Balducci et al., 2010).”
The importance of prion research
Eid, S., Lee, S., Verkuyl, C. E., Almanza, D. L., Hanna, J., Shenouda, S., Belotserkovsky, A., Zhao, W., & Watts, J. C. (2024) · Biochemistry and Cell Biology · doi:10.1139/bcb-2024-0018 · Cited by 8
Laboratory activities involving transmissible spongiform encephalopathy causing agents
Leunda, A., Vaerenbergh, B. V., Baldo, A., Roels, S., & Herman, P. (2013) · Prion · doi:10.4161/pri.26533 · Cited by 8
“However some conflicting reports exist where the effects of Aβ in memory properties have been shown to be independent of PrP.(20,21) Thus more research is needed to establish the link between PrP and Alzheimer disease.”
Applications for Treatment of Neurodegenerative Diseases
Ježek, J., Hlaváček, J., & Šebestı́k, J. (2017) · Progress in drug research · doi:10.1007/978-3-319-63953-6_6 · Cited by 7
Oligomeropathies, inflammation and prion protein binding
Forloni, G., Vitola, P. L., & Balducci, C. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.822420 · Cited by 8
“behavior; Aβ-antibody completely antagonized the AβO activity (Balducci et al., 2010).”
BackgroundSelf-citationHuang, Y., Xie, X.-X., Yang, J., Sun, X., Niu, X.-Y., Yang, C., Li, L., Zhang, L., Wang, D., Liu, C.-Y., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112624 · Cited by 9
Striatal pathology underlies prion infection-mediated hyperactivity in mice
Gunapala, K. M., Chang, D., Hsu, C. T., Manaye, K. F., Drenan, R. M., Switzer, R. C., & Steele, A. D. (2010) · Prion · doi:10.4161/pri.4.4.13721 · Cited by 8
Cell Line Specific Modulation of Extracellular Aβ42 by Hsp40
Carnini, A., Scott, L. O. M., Ahrendt, E., Proft, J., Winkfein, R. J., Kim, S.-W., Colicos, M. A., & Braun, J. E. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037755 · Cited by 8
“The cellular prion protein has been shown to act as a functional high affinity receptor for Ab42 [29–31] Strittmatter and colleagues report that association of PrP with Ab42 mediates downstream Ab42-impairement of hippocampal long term poten tiation and that AD transgenic mice lacking PrP accumulate Ab42 but have nor…”
BackgroundResultLaurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., & Strittmatter, S. M. (2010) · Nature · doi:10.1038/nature09218 · Cited by 8
Maladie d’Alzheimer, peptide β-amyloïde et synapses
Hémar, A., & Mulle, C. (2011) · médecine/sciences · doi:10.1051/medsci/2011278015 · Cited by 14
Pollen, D. A., Baker, S. P., Hinerfeld, D. A., Swearer, J. M., Evans, B. A., Evans, J. E., Caselli, R. J., Rogaeva, E. A., George‐Hyslop, P. S., & Moonis, M. (2010) · Alzheimer s Research & Therapy · doi:10.1186/alzrt55 · Cited by 7
So, R. W. L., Amano, G., Stuart, E., Amini, A. E., Aguzzi, A., Collingridge, G. L., & Watts, J. C. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012517 · Cited by 6
Telomeric DNA damage response mediates neurotoxicity of Aβ42 oligomers in Alzheimer’s disease
Sepe, S., Rey, F., Mancheno-Ferris, A., Bigi, A., Fani, G., Damiani, D., Cabrini, M., Marinelli, E., Aguado, J., Contu, L., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00521-1 · Cited by 7
“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 (Beeg et al, 2011; Balducci et al, 2010).”
Effects of Syzygium cumini Seed Extract on the Memory Loss of Alzheimer’s Disease Model Rats
Hossain, S., Islam, J., Bhowmick, S., Haque, M., & Rahaman, K. A. (2017) · Advances in Alzheimer s Disease · doi:10.4236/aad.2017.63005 · Cited by 7
“Intraventricular infusion of Aβ peptides leads to memory impairments in rats, with a corresponding lower levels of synaptic transmission and plasticity-related proteins like BDNF and PSD-95 [52] [53] [54].”
BackgroundFontana, I. C., Ferreira, P. C. L., Miron, D., Santos, L. E., Ferreira, S. T., Souza, D. O., Gosmann, G., Zimmer, E. R., & Zimmer, A. R. (2021) · Journal of Chromatography A · doi:10.1016/j.chroma.2021.462024 · Cited by 8
Common therapeutic strategies for prion and Alzheimer’s diseases
Elezgarai, S. R., & Biasini, E. (2016) · Biological Chemistry · doi:10.1515/hsz-2016-0190 · Cited by 7
“It is noteworthy that several studies have questioned the importance of PrPC in mediating Aβ toxicity, by reporting multiple experimental contexts in which Aβ toxicity was observed in absence of PrPC (Balducci et al., 2010; Calella et al., 2010; Kessels et al., 2010; Cisse et al., 2011).”
BackgroundSelf-citationMisfolded proteins as a therapeutic target in Alzheimer's disease
Liyanage, S. I., & Weaver, D. F. (2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2019.08.003 · Cited by 8
Relationship between efficacy and preferential targeting of soluble Aβ aggregates
Kaplan, J. M., Gibbs, E., Coutts, J. A., Zhao, B., Mackenzie, I. R., Plotkin, S. S., & Cashman, N. R. (2025) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.70184 · Cited by 6
Kumro, J., Tripathi, A., Lei, Y., Sword, J., Callahan, P. M., Terry, A. V., Lu, X., Kirov, S. A., Pillai, A., & Blake, D. T. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad066 · Cited by 6
Célestine, M., Jacquier‐Sarlin, M. R., Borel, E., Petit, F., Pérot, J., Hérard, A., Bousset, L., Buisson, A., & Dhénain, M. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01559-0 · Cited by 7
Potential Application of MicroRNAs and Some Other Molecular Biomarkers in Alzheimer’s Disease
Paprzycka, O., Wieczorek, J., Nowak, I., Madej, M., & Strzałka‐Mrozik, B. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46060304 · Cited by 7
“Furthermore, it is suggested that the relationship between the prion protein and β -amyloids is bidirectional, which may complicate the interpretation of test results related to these interactions [48].”
BackgroundResultInfluentialBoroujeni, E. R., Hosseini, S. M., Fani, G., Cecchi, C., & Chiti, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197273 · Cited by 7
“Even studies showing that PrPC-expressing and PrPC knock-out mice were equally susceptible to Aβ42 oligomer-induced cognitive impairment recognized that the oligomers interacted with PrPC with high affinity [19].”
BackgroundCellular prion protein offers neuroprotection in astrocytes submitted to amyloid β oligomer toxicity
Marques, C. M. S., Gomes, R. N., Pedron, T., Batista, B. L., & Cerchiaro, G. (2022) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-022-04631-w · Cited by 6
Optimized Ultrasonic Irradiation Finds Out Ultrastable Aβ1–40 Oligomers
Nakajima, K., So, M., Takahashi, K., Tagawa, Y., Hirao, M., Goto, Y., & Ogi, H. (2017) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.7b01409 · Cited by 7
Fukuda, A., Nakashima, S., Oda, Y., Nishimura, K., Kawashima, H., Kimura, H., Ohgita, T., Kawashita, E., Ishihara, K., Hanaki, A., et al. (2023) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b22-00797 · Cited by 5
Tapella, L., Dematteis, G., Vitola, P. L., Leva, S., Tonelli, E., Raddi, M., Delconti, M., Dacomo, L., Macchia, A. L., Murari, E., et al. (2024) · Glia · doi:10.1002/glia.24509 · Cited by 6
“We proved that a single ICV (intracerebroventricular) injection of A β Os produces memory impairment associated with a neuroinflammatory reaction (Balducci et al., 2010; Balducci et al., 2017; Balducci & Forloni, 2014).”
BackgroundMethodInfluentialSelf-citationMercer, R. C. C., McDonald, A. J., Bove‐Fenderson, E., Fang, C., Wu, B., & Harris, D. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811304-2.00002-x · Cited by 5
The Amyloid Precursor Protein: More than Just Amyloid- Beta
Jevtic, S. D., & Provias, J. (2019) · Journal of Neurology and Experimental Neuroscience · doi:10.17756/jnen.2019-045 · Cited by 5
Lima‐Filho, R. A. S., & Oliveira, M. M. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.3307-17.2018 · Cited by 5
“Although A Os may lead to memory failure through multiple mechanisms (Balducci et al., 2010), their interactions with PrP C have been shown to mediate aberrant signaling pathways, synapse loss, and cognitive decline in AD models (for review, see Salazar and Strittmatter, 2017).”
BackgroundNew light on prions: putative role of co-operation of PrPc and Aβ proteins in cognition
Chrobak, A. A., & Adamek, D. (2014) · Folia Neuropathologica · doi:10.5114/fn.2014.41739 · Cited by 5
“their interactions with PrPc [49], but other studies did not confirm this result [1,11].”
ResultThe Detection of Toxic Amyloid-β Fibril Fragments Through a Surface Plasmon Resonance Immunoassay
Beeg, M., Rocutto, B., Battocchio, E., Dacomo, L., Corbelli, A., Fiordaliso, F., Balducci, C., & Gobbi, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313020 · Cited by 5
Self-citationZhao, W., Toolan, D. M., Hepler, R. W., Wolfe, A. L., Yu, Y., Price, E. A., Uebele, V. N., Schachter, J. B., Reynolds, I. J., Renger, J. J., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-102022 · Cited by 4
Yoshiya, T., Maruno, T., Uemura, T., Kubo, S., Kiso, Y., Sohma, Y., Yoshizawa‐Kumagaye, K., Kobayashi, Y., & Nishiuchi, Y. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.06.052 · Cited by 4
Mamun, A. A. (2015) · Medical Entomology and Zoology · Cited by 4
Rapid ex vivo reverse genetics identifies the essential determinants of prion protein toxicity
Reimann, R. R., Puzio, M., Rosati, A., Emmenegger, M., Schneider, B. L., Valdés, P., Huang, D., Caflisch, A., & Aguzzi, A. (2023) · Brain Pathology · doi:10.1111/bpa.13130 · Cited by 3
“Several studies have reported a high-affinity interaction of the CC2 with amyloid-β (Aβ) oligomers [8, 33].”
BackgroundA New Interpretative Paradigm for Conformational Protein Diseases
Agnati, L. F., Guidolin, D., Woods, A. S., Ciruela, F., Carone, C., Vallelunga, A., Escuela, D. O. B., Genedani, S., & Fuxé, K. (2013) · Current Protein and Peptide Science · doi:10.2174/1389203711314020006 · Cited by 4
White, J. D., Urbano, C. M., Taylor, J. O., Peterman, J. L., Cooksey, M., Eimerbrink, M. J., Eriksson, M. D., Cooper, B. G., Chumley, M. J., & Boehm, G. W. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112303 · Cited by 4
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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