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Aβ40 Inhibits Amyloid Deposition In Vivo
Open accessAbstract
Numerous studies have established a pivotal role for Aβ42 in Alzheimer's disease (AD) pathogenesis. In contrast, although Aβ40 is the predominant form of amyloid β (Aβ) produced and accumulates to a variable degree in the human AD brain, its role in AD pathogenesis has not been established. It has generally been assumed that an increase in Aβ40 would accelerate amyloid plaque formation in vivo. We have crossed BRI-Aβ40 mice that selectively express high levels of Aβ40 with both Tg2576 (APPswe, K670N+M671L) mice and BRI-Aβ42A mice expressing Aβ42 selectively and analyzed parenchymal and cerebrovascular Aβ deposition in the bitransgenic mice compared with their singly transgenic littermates. In the bitransgenic mice, the increased steady-state levels of Aβ40 decreased Aβ deposition by 60–90%. These results demonstrate that Aβ42 and Aβ40 have opposing effects on amyloid deposition: Aβ42 promotes amyloid deposition but Aβ40 inhibits it. In addition, increasing Aβ40 levels protected BRI-Aβ40/Tg2576 mice from the premature-death phenotype observed in Tg2576 mice. The protective properties of Aβ40 with respect to amyloid deposition suggest that strategies that preferentially target Aβ40 may actually worsen the disease course and that selective increases in Aβ40 levels may actually reduce the risk for development of AD.
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TL;DR
Increasing Aβ40 levels in transgenic mouse models reduced parenchymal and vascular amyloid deposition, contrary to the assumption that Aβ40 promotes plaque formation. Aβ40 directly inhibited Aβ42 aggregation in vitro and also reduced premature death in BRI-Aβ40/Tg2576 mice.
Key findings
- In BRI-Aβ40/Tg2576 mice, increased steady-state Aβ40 levels decreased Aβ deposition by 60–90%; RIPA-insoluble, formic acid-extractable Aβ40 and Aβ42 levels were reduced by 60–80% in forebrain and hindbrain, and CAA severity score and affected leptomeningeal vessels decreased by ~60 and ~30% at 15 and 20 months, respectively.
- In BRI-Aβ40/BRI-Aβ42A mice at 8 months, Aβ plaque burden, ThioS-positive cored plaques in cerebellum, and formic acid-extractable Aβ42 were significantly decreased by ~75%, despite soluble brain Aβ (Aβ40 plus Aβ42) being increased ~10-fold compared with BRI-Aβ42A littermates.
- Premature death was modulated by Aβ: BRI-Aβ40/BRI-Aβ42A mice approached 100% death by 16 months, BRI-Aβ42A/Tg2576 mice had ~50% premature death versus ~30% in Tg2576 littermates, while BRI-Aβ40/Tg2576 mice had ~10% death at 7 months.
- In vitro, adding Aβ40 to Aβ42 reduced formation of high-molecular-weight Aβ42 aggregates, leaving most Aβ42 as low-molecular-weight species.
Methods
- Hemizygous BRI-Aβ40 mice were crossed with Tg2576 (APPswe) mice and with BRI-Aβ42A or BRI-Aβ42B mice; littermates were compared across aging series (8–20 months), with n = 5–7 mice per genotype at each age group.
- Parenchymal amyloid burden and ThioS-positive cored plaques were quantified by immunohistochemistry; CAA was scored in leptomeningeal vessels; Aβ levels were measured by sandwich ELISA; APP/C99 levels by Western blot; survival by Kaplan-Meier analysis; and Aβ aggregation by nondenaturing gel assay with synthetic Aβ40/Aβ42 peptides.
- Statistical analyses used ANOVA with Holm-Sidak post hoc tests, t tests, nonparametric tests where needed, and multiple linear regression with no intercept to test additive Aβ levels.
Limitations
- The paper states that extensive premature death in BRI-Aβ40/BRI-Aβ42A mice limited rigorous pathological analyses to an 8-month time point.
- The paper states that it is difficult to completely exclude other transgene-related and genetic background effects, and that premature death rate/extent is influenced by total Aβ levels, Aβ40:Aβ42 ratio, and genetic background.
- The paper states that additional studies are needed to understand factors promoting Aβ40 accumulation within vessels and to investigate effects of increased Aβ40 on oligomer formation and behavioral abnormalities; evident from the text, the work is in mouse models and in vitro assays, with no human AD cohort or cognitive/behavioral therapeutic testing reported.
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34 Own result · 5 No full text of the sources · 4 Own interpretation · 2 Not checked yet · 1 Supported · 1 No basis given
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In the paper
“accumulates to a variable degree in the human AD brain”
- Also stated in: § Introduction · plain
“A40 does accumulate in the AD brain, but the extent of A40 accumulation relative to A42 is highly variable and is usually attributed to accumulation of A40 in cerebral vessels (Gravina et al., 1995).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Abstract
What the sources say
- Supportedcites Gravina et al., 1995 source
The paper’s opening summary reports that 18 of 27 AD brains contained increasing amounts of Aβ ending at Aβ40. It also says that widely varying amounts were deposited in the remaining AD brains, primarily in blood vessel walls. (LLM, conf=0.94)
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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- Also stated in: § Introduction · 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
“There was a significant decrease in both the A plaque burden and number of ThioS-positive plaques in BRI-A40/Tg2576 mice compared with Tg2576 littermates ( p Ͻ 0.05).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Extensive premature death observed in BRI-A40/BRI-A42A mice limited rigorous pathological analyses to an 8 month time point (see Fig.7A).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
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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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
“There was a significant decrease in both the A plaque burden and number of ThioS-positive plaques in BRI-A40/Tg2576 mice compared with Tg2576 littermates ( p Ͻ 0.05).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plain- 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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In the paper
“BRI-A42A/Tg2576 mice had a significantly increased premature death rate compared with Tg2576 littermates ( p Ͻ 0.05).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plaincorrelational- 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
“A, RIPA-insoluble, FA-extractable A40 and A42 levels in the forebrain of BRI-A40/Tg2576 were significantly reduced compared with Tg2576 littermates at all ages (A40 levels at p ϭ 0.01, p Ͻ 0.001, and p Ͻ 0.001 at 11, 15, and 20 months, respectively, and A42 levels at p Ͻ 0.001 at all age).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plaincorrelational- 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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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
“There was no difference in survival rates for Tg2576 progeny from breeding with either BRI-A40 mice or BRI-A42A mice ( p ϭ 0.884), thus Tg2576 data were pooled.”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
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
“At this age, A plaque burden, the number of ThioS-positive cored plaques in the cerebellum, and FA-fraction A42 levels were significantly decreased by ϳ75% in BRI-A40/BRI-A42A mice (Fig.4), although steady-state soluble brain A (A40 plus A42) levels were increased by ϳ10-fold in bitransgenic mice compared with BRI-A42A littermates (Fig.5D).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
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.
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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
“At this age, A plaque burden, the number of ThioS-positive cored plaques in the cerebellum, and FA-fraction A42 levels were significantly decreased by ϳ75% in BRI-A40/BRI-A42A mice (Fig.4), although steady-state soluble brain A (A40 plus A42) levels were increased by ϳ10-fold in bitransgenic mice compared with BRI-A42A littermates (Fig.5D).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plaindirect- 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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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, RIPA-insoluble, FA-extractable A40 and A42 levels in the forebrain of BRI-A40/Tg2576 were significantly reduced compared with Tg2576 littermates at all ages (A40 levels at p ϭ 0.01, p Ͻ 0.001, and p Ͻ 0.001 at 11, 15, and 20 months, respectively, and A42 levels at p Ͻ 0.001 at all age).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plaincorrelational- 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.
- It may state two separate claims as one. 7
- Probably not a substantial claim. 6
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
“Bitransgenic BRI-A40/BRI-A42A had an accelerated mortality, whereas non-Tg, single transgenic BRI-A40, and BRI-A42A mice did not show any premature death ( p Ͻ 0.01).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plain- 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
“Although BRI-A40/Tg2576 only had 10% premature death at 7 months of age, Tg2576 mice had ϳ30% early death ( p Ͻ 0.01).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
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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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
“Decreased FA-A40 levels were also detected but did not reach statistical significance ( p ϭ 0.101 by rank sum test).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
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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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
“After a 2 h incubation, the A42-only preparation (A40:A42 ratio; 0:1) formed very high molecular weight (HMW) aggregates (indicated by”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plain- 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.
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 A40 was mixed with A42 (A40:A42 ratio; 0.5:1 and 1:1), A40 inhibited the formation of HMW A42 aggregates, and the vast majority of A42 remained as LMW species (indicated by 4 at the bottom of the blot).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
plaindirect- 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
“In vivo, A42 is the predominant form of A that accumulates in the AD brain and is essential for seeding A deposition (Younkin, 1998;Fryer and Holtzman, 2005).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Introduction
What the sources say
- Not checked — no full text of the sourcecites Younkin, 1998 source
- Not matchedcites Fryer and Holtzman, 2005
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
In the paper
“-Synuclein inhibits ␣-synuclein aggregation in mice, and mouse tau may retard human tau aggregation (Rochet et al., 2000;Hashimoto et al., 2001;Andorfer et al., 2003).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
What the sources say
- Not checked — no full text of the sourcecites Hashimoto et al., 2001 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.
In the paper
“although A40 is the predominant form of amyloid  (A) produced”
- Also stated in: § Introduction · plain
“Sequential amyloid  precursor protein (APP) processing by -secretase and ␥-secretase produces a major A species, A1-40, and a number of minor species, including A1-42 (Steiner and Haass, 2000).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Abstract
What the sources say
- Not checked — no full text of the sourcecites Steiner and Haass, 2000 source
plain- 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.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Introduction · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The inhibition of amyloid deposition by A40 may have critical implications for AD therapy.”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions 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.
- Rests on an assumption: Findings in transgenic mouse models of amyloid deposition are relevant to human Alzheimer's disease therapy.
None of the sources cited for this claim have been checked yet.
In the paper
“BRI-A42A mice initially develop amyloid deposition in the cerebellum at ϳ3 months of age, whereas forebrain pathology was consistently observed only after ϳ12 months of age(McGowan et al., 2005).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
What the sources say
- Not checked yetcites McGowan et al., 2005 source
Checked before — its earlier verdict is held back until a new check runs.
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not checked yet
In the paper
“-Synuclein inhibits ␣-synuclein aggregation in mice, and mouse tau may retard human tau aggregation (Rochet et al., 2000;Hashimoto et al., 2001;Andorfer et al., 2003).”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Discussion
What the sources say
- Not checked — no full text of the sourcecites Andorfer et al., 2003 source
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.
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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
“its role in AD pathogenesis has not been established”
§ Neurobiology of Disease A40 Inhibits Amyloid Deposition In Vivo > Abstract
plain- 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.
Probably not a substantial claim.
The paper relies on this without support.
Findings in transgenic mouse models of amyloid deposition are relevant to human Alzheimer's disease therapy.
“The inhibition of amyloid deposition by A40 may have critical implications for AD therapy.”
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“By crossing BRI2-A1-40 or BRI-A1-42 transgenic mice with Tg2576 mice, we previously demonstrated that A1-40 and A42 have opposing effects on amyloid deposition (McGowan et al., 2005;Kim et al., 2007).”
From BRI2 (ITM2b) Inhibits A Deposition In Vivo (2008) · cites this paper as Kim et al., 2007
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Aβ40 is present in larger amounts in the brain, yet Aβ42 is more neurotoxic and has a higher tendency to aggregate.8–11”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Almost all previous studies investigating the effect of bifunctional compounds on the neurotoxicity of metal-Aβ species have focused on the less neurotoxic and possibly even anti-amyloidogenic Aβ40 peptide.9,97,98”
From Bifunctional Compounds for Controlling Metal-Mediated Aggregation of the Aβ42Peptide (2012) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Aβ species, including the most abundant Aβ40 and more toxic Aβ42, are produced by two sequential proteolytic cleavages of amyloid precursor protein (APP) by β- and γ-secretases (Kim et al., 2007; McGowan et al., 2005).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Kim et al., 2007
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Several methods were used, including a native gel assay previously used to demonstrate that A1-40 inhibits A1-42 aggregation (Kim et al., 2007).”
From BRI2 (ITM2b) Inhibits A Deposition In Vivo (2008) · cites this paper as Kim et al., 2007
The cited source says what the claim attributes to it.
In the citing paper
“The reduction in A deposition observed in the mice expressing the rAAV1 BRI2-A1-40 transgene was consistent with our previous transgenic mice studies (Kim et al., 2007), whereas the reduction of A deposition observed in the mice expressing BRI2 was unexpected.”
From BRI2 (ITM2b) Inhibits A Deposition In Vivo (2008) · cites this paper as Kim et al., 2007
The cited source says what the claim attributes to it.
In the citing paper
“The studies with BRI2-A1-40 confirmed previous studies obtained using conventional transgenic mice expressing BRI2-A1-40 (McGowan et al., 2005;Kim et al., 2007).”
From BRI2 (ITM2b) Inhibits A Deposition In Vivo (2008) · cites this paper as Kim et al., 2007
The cited source says what the claim attributes to it.
In the citing paper
“Such high concentrations may artificially cause Aβ40 to aggregate without an Aβ42 seeding nucleus, despite the fact that Aβ40 has an anti-amyloidogenic effect in vivo (Kim et al., 2007).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Kim et al., 2007
The cited source says what the claim attributes to it.
In the citing paper
“Several recent studies suggest that Aβ40 and Aβ42 may have opposing effects on Aβ aggregation in vivo (Kim et al., 2007; McGowan et al., 2005).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Kim et al., 2007
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Cited works that were retracted
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In the paper
“…2003; Lombardo et al., 2003; Tsai et al., 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synaptic dysfunction and memory deficits in mice (Klein et al., 2004; Cleary et al., 2005; Glabe, 2006; Lesne et al., 2006).”
Cited work 10.1038/nature04533 · retracted 2024-06-24 · notice 10.1038/s41586-024-07691-8 · this paper published 2007-01-17
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 · cited 1×
“…2003; Lombardo et al., 2003; Tsai et al., 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synaptic dysfunction and memory deficits in mice (Klein et al., 2004; Cleary et al., 2005; Glabe, 2006; Lesne et al., 2006).”
BackgroundRetractedThe Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · cited 3×
“…BRI-A 40/Tg2576 mice We crossed hemizygous BRI-A 40 mice that produce only A 40 with hemizygous APPswe (Tg2576) mice overexpressing a normal profile of human A peptides (Hsiao et al., 1996), generating offspring with nontransgenic (non-Tg), BRI-A 40, Tg2576, and BRI-A 40/Tg2576 genotypes.”
BackgroundMethodInfluentialMucke, 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 · cited 1×
“Finally, results from transgenic mice expressing wild-type and various mutant forms of APP also suggest that increased A 40 levels might reduce amyloid deposition (Mucke et al., 2000).”
BackgroundNatural 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 · cited 2×
“, 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synaptic dysfunction and memory deficits in mice (Klein et al., 2004; Cleary et al., 2005; Glabe, 2006; Lesne et al., 2006).”
BackgroundCaughey, B., & Lansbury, P. T. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.010302.081142 · Cited by 1,650 · cited 3×
“In vitro, A 42 aggregates into amyloid much more rapidly than A 40 (Caughey and Lansbury, 2003).”
BackgroundA subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity
Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., et al. (2001) · Nature · doi:10.1038/35102591 · Cited by 1,388 · cited 1×
“Our data support the strategy that selectively targeting A 42 by allosterically modulating -secretase may be preferential to nonselective inhibition of -secretase activity (Weggen et al., 2001; Eriksen et al., 2003; Lleo et al., 2004).”
MethodSelf-citationKawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · cited 2×
“3 (anti-A 35-42 Ab) as the capture Ab for A 42, and Ab9 –HRP as the detection Ab for A 42, as described previously (Kawarabayashi et al., 2001) (n 5–7 mice per genotype at each age group).”
MethodInfluentialLeissring, M. A., Farris, W., Chang, A. Y., Walsh, D. M., Wu, X., Sun, X., Frosch, M. P., & Selkoe, D. J. (2003) · Neuron · doi:10.1016/s0896-6273(03)00787-6 · Cited by 725
Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms
Andorfer, C., Kress, Y., Espinoza, M., De Silva, R., Tucker, K. L., Barde, Y., Duff, K., & Davies, P. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01879.x · Cited by 722 · cited 1×
“-Synuclein inhibits -synuclein aggregation in mice, and mouse tau may retard human tau aggregation (Rochet et al., 2000; Hashimoto et al., 2001; Andorfer et al., 2003).”
BackgroundAmyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7013 · Cited by 676 · cited 2×
“This is a surprising result given that A 40 is reported to be the predominant A species deposited in vessels (Gravina et al., 1995).”
BackgroundMoechars, D., Dewachter, I., Lorent, K., Reversé, D., Baekelandt, V., Naidu, A., Tesseur, I., Spittaels, K., Haute, C. V. D., Checler, F., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6483 · Cited by 668 · cited 3×
“In contrast to many lines of mutant APP mice that exhibit a premature-death phenotype (Moechars et al., 1999b; Leissring et al., 2003), BRI-A 40 or BRI-A 42 mice did not have accelerated mortality (Fig.”
BackgroundResultNSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
Eriksen, J. L., Sagi, S. A., Smith, T. E., Weggen, S., Das, P., McLendon, D. C., Ozols, V. V., Jessing, K. W., Zavitz, K. H., Koo, E. H., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18162 · Cited by 634 · cited 1×
“Our data support the strategy that selectively targeting A 42 by allosterically modulating -secretase may be preferential to nonselective inhibition of -secretase activity (Weggen et al., 2001; Eriksen et al., 2003; Lleo et al., 2004).”
MethodCommon mechanisms of amyloid oligomer pathogenesis in degenerative disease
Glabe, C. G. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.04.017 · Cited by 569 · cited 2×
“, 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synaptic dysfunction and memory deficits in mice (Klein et al., 2004; Cleary et al., 2005; Glabe, 2006; Lesne et al., 2006).”
BackgroundAβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice
McGowan, E., Pickford, F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.030 · Cited by 565 · cited 16×
“BRI-A 42A mice led to a reduction in CAA, demonstrating that A 40 has anti-amyloidogenic effects on not only parenchymal but also vascular amyloid deposition.”
BackgroundMethodInfluentialSelf-citationFibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches
Tsai, J., Grutzendler, J., Duff, K., & Gan, W.-B. (2004) · Nature Neuroscience · doi:10.1038/nn1335 · Cited by 561 · cited 2×
“…debate regarding the role of amyloid in AD pathogenesis (Le et al., 2001; Caughey and Lansbury, 2003; D’Amore et al., 2003; Lombardo et al., 2003; Tsai et al., 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the…”
BackgroundHsiao, K., Borchelt, D., Olson, K., Johannsdottir, R., Kitt, C. A., Yunis, W. S., Xu, S., Eckman, C., Younkin, S. G., Price, D., et al. (1995) · Neuron · doi:10.1016/0896-6273(95)90107-8 · Cited by 526 · cited 1×
“Premature death has been observed in many mutant APP transgenic mice on multiple background strains, although no one has been able to determine the cause of death (Hsiao et al., 1995; Moechars et al., 1999b; Leissring et al., 2003).”
BackgroundKlein, W. L., Stine, W. B., & Teplow, D. B. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.010 · Cited by 494 · cited 2×
“, 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synaptic dysfunction and memory deficits in mice (Klein et al., 2004; Cleary et al., 2005; Glabe, 2006; Lesne et al., 2006).”
BackgroundPresenilin clinical mutations can affect γ‐secretase activity by different mechanisms
Bentahir, M., Nyabi, O., Verhamme, J., Tolia, A., Horré, K., Wiltfang, J., Esselmann, H., & Strooper, B. D. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03578.x · Cited by 427 · cited 1×
“Decreases in A 40, without an increase in A 42, have been associated with a subset of AD causing PSEN mutations and the APPV715M mutation (Ancolio et al., 1999; Bentahir et al., 2006; Kumar-Singh et al., 2006).”
BackgroundALZHEIMER'S DISEASE: Genetic Studies and Transgenic Models
Price, D. L., Tanzi, R. E., Borchelt, D. R., & Sisodia, S. S. (1998) · Annual Review of Genetics · doi:10.1146/annurev.genet.32.1.461 · Cited by 406 · cited 1×
“Studies of AD-causing mutations in APP, presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes demonstrate that the vast majority of these mutations alter APP processing in a manner that either increases the absolute or relative levels of A 42 (Price et al., 1998).”
Backgroundβ-Synuclein Inhibits α-Synuclein Aggregation
Hashimoto, M., Rockenstein, E., Mante, M., Mallory, M., & Masliah, E. (2001) · Neuron · doi:10.1016/s0896-6273(01)00462-7 · Cited by 398 · cited 1×
“-Synuclein inhibits -synuclein aggregation in mice, and mouse tau may retard human tau aggregation (Rochet et al., 2000; Hashimoto et al., 2001; Andorfer et al., 2003).”
BackgroundHerzig, M. C., Winkler, D. T., Burgermeister, P., Pfeifer, M., Kohler, E., Schmidt, S. D., Danner, S., Abramowski, D., Stürchler-Pierrat, C., Bürki, K., et al. (2004) · Nature Neuroscience · doi:10.1038/nn1302 · Cited by 391 · cited 1×
“Although previous studies suggested that a higher ratio of A 40 to A 42 might promote the formation of CAA over parenchymal deposition (Herzig et al., 2004; Fryer and Holtzman, 2005; Fryer et al., 2005), in other studies, selective increases in A 42 were associated with more CAA (Van Dorpe et al.,…”
ResultSnyder, S. W., Ladror, U. S., Wade, W. S., Wang, G. T., Barrett, L. W., Matayoshi, E. D., Huffaker, H. J., Krafft, G. A., & Holzman, T. F. (1994) · Biophysical Journal · doi:10.1016/s0006-3495(94)80591-0 · Cited by 381 · cited 2×
“There are several in vitro studies demonstrating that A 40 directly interferes with A 42 aggregation by delaying the A 42- mediated nucleation step at an early stage in the fibrillogenesis process (Snyder et al., 1994; Hasegawa et al., 1999; Zou et al., 2003).”
BackgroundTherapeutic effects of PKC activators in Alzheimer's disease transgenic mice
Etcheberrigaray, R., Tan, M., Dewachter, I., Kuipéri, C., der Auwera, I. V., Wera, S., Qiao, L., Bank, B., Nelson, T. J., Kozikowski, A. P., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403921101 · Cited by 343 · cited 1×
“Reduction in A levels by increased -secretase activity or by enhanced proteolysis of A has been linked to prevention of high mortality in APP transgenic mice and Drosophila (Leissring et al., 2003; Etcheberrigaray et al., 2004; Finelli et al., 2004).”
BackgroundKumar‐Singh, S., Theuns, J., Broeck, B. V., Pirici, D. N., Vennekens, K., Corsmit, E., Cruts, M., Dermaut, B., Wang, R., & Broeckhoven, C. V. (2006) · Human Mutation · doi:10.1002/humu.20336 · Cited by 330 · cited 1×
“Decreases in A 40, without an increase in A 42, have been associated with a subset of AD causing PSEN mutations and the APPV715M mutation (Ancolio et al., 1999; Bentahir et al., 2006; Kumar-Singh et al., 2006).”
BackgroundDiagnosis of Cerebral Amyloid Angiopathy: Sensitivity and Specificity of Cortical Biopsy
Greenberg, S. M., & Vonsattel, J.-P. G. (1997) · Stroke · doi:10.1161/01.str.28.7.1418 · Cited by 312 · cited 1×
“Positively stained blood vessels were visually assessed using modified Vonsattel’s scoring system as described previously (Greenberg and Vonsattel, 1997).”
MethodA model for studying Alzheimer's Aβ42-induced toxicity in Drosophila melanogaster
Finelli, A. L., Kelkar, A., Song, H., Yang, H., & Konsolaki, M. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.03.001 · Cited by 299 · cited 1×
“Reduction in A levels by increased -secretase activity or by enhanced proteolysis of A has been linked to prevention of high mortality in APP transgenic mice and Drosophila (Leissring et al., 2003; Etcheberrigaray et al., 2004; Finelli et al., 2004).”
BackgroundThe role of Aβ42 in Alzheimer's disease
Younkin, S. G. (1998) · Journal of Physiology-Paris · doi:10.1016/s0928-4257(98)80035-1 · Cited by 282 · cited 1×
“In vivo, A 42 is the predominant form of A that accumulates in the AD brain and is essential for seeding A deposition (Younkin, 1998; Fryer and Holtzman, 2005).”
BackgroundFryer, J. D., Simmons, K., Parsadanian, M., Bales, K. R., Paul, S. M., Sullivan, P. M., & Holtzman, D. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5170-04.2005 · Cited by 278 · cited 2×
“In vivo, A 42 is the predominant form of A that accumulates in the AD brain and is essential for seeding A deposition (Younkin, 1998; Fryer and Holtzman, 2005).”
BackgroundResultLashuel, H. A., Hartley, D. M., Petre, B. M., Wall, J. S., Simon, M. N., Walz, T., & Lansbury, P. T. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00927-6 · Cited by 240 · cited 1×
“Additional studies have shown that wild-type A 40 can stabilize aggregation of Arctic mutant A 40 (E22G) (Lashuel et al., 2003).”
BackgroundDorpe, J. V., Smeijers, L., Dewachter, I., Nuyens, D., Spittaels, K., den Haute, C. V., Mercken, M. H., Moechars, D., Laenen, I., Kuipéri, C., et al. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64644-5 · Cited by 223 · cited 1×
“…of A 40 to A 42 might promote the formation of CAA over parenchymal deposition (Herzig et al., 2004; Fryer and Holtzman, 2005; Fryer et al., 2005), in other studies, selective increases in A 42 were associated with more CAA (Van Dorpe et al., 2000; Samura et al., 2006; Van Dooren et al., 2006).”
ResultRochet, J., Conway, K. A., & Lansbury, P. T. (2000) · Biochemistry · doi:10.1021/bi001315u · Cited by 221
Interaction between Aβ(1−42) and Aβ(1−40) in Alzheimer's β-Amyloid Fibril Formation in Vitro
Hasegawa, K., Yamaguchi, I., Omata, S., Gejyo, F., & Naiki, H. (1999) · Biochemistry · doi:10.1021/bi991161m · Cited by 198 · cited 1×
“There are several in vitro studies demonstrating that A 40 directly interferes with A 42 aggregation by delaying the A 42- mediated nucleation step at an early stage in the fibrillogenesis process (Snyder et al., 1994; Hasegawa et al., 1999; Zou et al., 2003).”
BackgroundNonsteroidal anti-inflammatory drugs lower Aβ42 and change presenilin 1 conformation
Lleó, A., Berezovska, O., Herl, L. D., Raju, S., Deng, A., Bacskai, B. J., Frosch, M. P., Irizarry, M. C., & Hyman, B. T. (2004) · Nature Medicine · doi:10.1038/nm1112 · Cited by 198
Ancolio, K., Dumanchin‐Njock, C., Barelli, H., Warter, J., Brice, A., Campion, D., Frébourg, T., & Checler, F. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.4119 · Cited by 183 · cited 1×
“Decreases in A 40, without an increase in A 42, have been associated with a subset of AD causing PSEN mutations and the APPV715M mutation (Ancolio et al., 1999; Bentahir et al., 2006; Kumar-Singh et al., 2006).”
BackgroundIntramembrane proteolysis by presenilins
Steiner, H., & Haass, C. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043065 · Cited by 161 · cited 1×
“Sequential amyloid precursor protein (APP) processing by -secretase and -secretase produces a major A species, A 1-40, and a number of minor species, including A 1-42 (Steiner and Haass, 2000).”
BackgroundZou, K., Kim, D. S., Kakio, A., Byun, K., Gong, J., Kim, J. W., Kim, M. J., Sawamura, N., Nishimoto, S., Matsuzaki, K., et al. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02018.x · Cited by 160 · cited 1×
“There are several in vitro studies demonstrating that A 40 directly interferes with A 42 aggregation by delaying the A 42- mediated nucleation step at an early stage in the fibrillogenesis process (Snyder et al., 1994; Hasegawa et al., 1999; Zou et al., 2003).”
BackgroundSelf-citationPotential role of presenilin-regulated signaling pathways in sporadic neurodegeneration
Koo, E. H., & Kopan, R. (2004) · Nature Medicine · doi:10.1038/nm1065 · Cited by 154 · cited 1×
“In addition, mutations in PSEN can have a variety of effects on protein trafficking, clearance, and intracellular signaling (Koo and Kopan, 2004; Zhang et al., 2006).”
BackgroundAmyloid-β Antibody Treatment Leads to Rapid Normalization of Plaque-Induced Neuritic Alterations
Lombardo, J. A., Stern, E. A., McLellan, M. E., Kajdasz, S. T., Hickey, G. A., Bacskai, B. J., & Hyman, B. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10879.2003 · Cited by 149 · cited 2×
“Although there is much debate regarding the role of amyloid in AD pathogenesis (Le et al., 2001; Caughey and Lansbury, 2003; D’Amore et al., 2003; Lombardo et al., 2003; Tsai et al., 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synapt…”
BackgroundMatsuda, S., Giliberto, L., Matsuda, Y., Davies, P., McGowan, E., Pickford, F., Ghiso, J., Frangione, B., & D'Adamio, L. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500217200 · Cited by 141 · cited 1×
“M, Months. creased A and increased C99 levels, with inconclusive effects of BRI on full-length APP and total secreted APP levels (Fotinopoulou et al., 2005; Matsuda et al., 2005).”
BackgroundSelf-citationNSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
Eriksen, J. L., Sagi, S. A., Smith, T. E., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200318162 · Cited by 135
BRI2 Interacts with Amyloid Precursor Protein (APP) and Regulates Amyloid β (Aβ) Production
Fotinopoulou, A., Tsachaki, M., Vlavaki, M., Poulopoulos, A., Rostagno, A., Frangione, B., Ghiso, J., & Efthimiopoulos, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.c500231200 · Cited by 114 · cited 1×
“M, Months. creased A and increased C99 levels, with inconclusive effects of BRI on full-length APP and total secreted APP levels (Fotinopoulou et al., 2005; Matsuda et al., 2005).”
BackgroundKlug, G. M., Lošić, D., Supundi, Subasinghe, S., Aguilar, M., Martin, L. L., & Small, D. H. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03815.x · Cited by 109 · cited 2×
“Mixtures were run on 4 –20% Tris-HCl gels under nondenaturing conditions and transferred to a 0.4 m polyvinylidene difluoride membrane as described previously (Klug et al., 2003).”
MethodInfluentialLe, R., Cruz, L., Urbanc, B., Knowles, R. B., Ashe, K. H., Duff, K., Irizarry, M. C., Stanley, E., & Hyman, B. T. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.8.753 · Cited by 90 · cited 2×
“Although there is much debate regarding the role of amyloid in AD pathogenesis (Le et al., 2001; Caughey and Lansbury, 2003; D’Amore et al., 2003; Lombardo et al., 2003; Tsai et al., 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synapt…”
BackgroundD'Amore, J. D., Kajdasz, S. T., McLellan, M. E., Bacskai, B. J., Stern, E. A., & Hyman, B. T. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.2.137 · Cited by 89 · cited 2×
“Although there is much debate regarding the role of amyloid in AD pathogenesis (Le et al., 2001; Caughey and Lansbury, 2003; D’Amore et al., 2003; Lombardo et al., 2003; Tsai et al., 2004), an increasing body of evidence suggests that soluble oligomeric and protofibrillar A species, such as A *56, may cause the synapt…”
BackgroundMoechars, D., Lorent, K., & Leuven, F. V. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00599-5 · Cited by 69 · cited 3×
“In contrast to many lines of mutant APP mice that exhibit a premature-death phenotype (Moechars et al., 1999b; Leissring et al., 2003), BRI-A 40 or BRI-A 42 mice did not have accelerated mortality (Fig.”
BackgroundResultDeng, Y., Tarassishin, L., Kallhoff, V., Peethumnongsin, E., Wu, L., Li, Y., & Zheng, H. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5384-05.2006 · Cited by 64 · cited 1×
“Small reductions in brain A 40 levels, with no change in A 42 levels, resulting from expression of an artificial exon 10 deletion mutant PSEN1 transgene were also associated with exacerbated amyloid plaque pathology in Tg2576 mice (Deng et al., 2006).”
BackgroundPresenilin/γ‐secretase activity regulates protein clearance from the endocytic recycling compartment
Zhang, M., Haapasalo, A., Kim, D. Y., Ingano, L. A. M., Pettingell, W. H., & Kovacs, D. M. (2006) · The FASEB Journal · doi:10.1096/fj.05-5531fje · Cited by 58 · cited 1×
“In addition, mutations in PSEN can have a variety of effects on protein trafficking, clearance, and intracellular signaling (Koo and Kopan, 2004; Zhang et al., 2006).”
BackgroundDooren, T. V., Muyllaert, D., Borghgraef, P., Cresens, A., Devijver, H., der Auwera, I. V., Wera, S., Dewachter, I., & LEUVEN, F. V. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050752 · Cited by 35 · cited 2×
“…of A 40 to A 42 might promote the formation of CAA over parenchymal deposition (Herzig et al., 2004; Fryer and Holtzman, 2005; Fryer et al., 2005), in other studies, selective increases in A 42 were associated with more CAA (Van Dorpe et al., 2000; Samura et al., 2006; Van Dooren et al., 2006).”
ResultEnhanced accumulation of tau in doubly transgenic mice expressing mutant βAPP and presenilin-1
Samura, E., Shoji, M., Kawarabayashi, T., Sasaki, A., Matsubara, E., Murakami, T., Wuhua, X., Tamura, S., Ikeda, M., Ishiguro, K., et al. (2006) · Brain Research · doi:10.1016/j.brainres.2005.12.134 · Cited by 33 · cited 1×
“…of A 40 to A 42 might promote the formation of CAA over parenchymal deposition (Herzig et al., 2004; Fryer and Holtzman, 2005; Fryer et al., 2005), in other studies, selective increases in A 42 were associated with more CAA (Van Dorpe et al., 2000; Samura et al., 2006; Van Dooren et al., 2006).”
ResultKrezowski, J. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh210 · Cited by 26 · cited 1×
“Together, these studies provide indirect evidence that alterations in A levels can modulate the premature-death phenotype, although one study sug- gests that this is not because of A (Krezowski et al., 2004).”
BackgroundThe Bad Seed in Alzheimer’s Disease
Fryer, J. D., & Holtzman, D. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.07.002 · Cited by 20 · cited 2×
“In vivo, A 42 is the predominant form of A that accumulates in the AD brain and is essential for seeding A deposition (Younkin, 1998; Fryer and Holtzman, 2005).”
BackgroundResultKlein, W. L. (2004) · Neurobiology of Aging · doi:10.1016/s0197-4580(04)00089-2 · Cited by 18
Dorpe, J. A. V., Smeijers, L., Dewachter, I., Spittaels, K., den Haute, C. V., Tesseur, I. C., Sciot, R., & LEUVEN, F. V. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)82614-7 · Cited by 10
Kumar‐Singh, S., Theuns, J., Broeck, B. V., et al. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2006.05.1665
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“Ab42, Ab43, and longer Ab peptides are highly self-aggregating, whereas Ab40 may actually be antiamyloidogenic (Kim et al, 2007).”
BackgroundKarran, E., Mercken, M., & Strooper, B. D. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3505 · Cited by 2,188
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Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
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“…and Aβ amyloid fibrils were present in Aβ42-overexpressing BRI2-Aβ mice, and amyloid deposits and formation of senile plaques were observed in the brain, degeneration of nerve cells and neuronal loss were not observed, and there was no impairment of cognitive functions (Kim et al., 2007, 2013).”
Background
Metadata
- Authors
- Kim, J., Onstead, L., Randle, S., Price, R., Smithson, L., Zwizinski, C., Dickson, D. W., Golde, T., & McGowan, E.
- Affiliations
- Mayo Clinic (US)
- Mayo Clinic in Florida (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-01-17
- Volume
- 27
- Issue
- 3
- Pages
- 627-633
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672801
- OpenAlex
- W2016811754
- Semantic Scholar
- cdc788c9481c38fa796d91320b21decd840d7619
- Cited by
- 359
- References
- 52
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 17 · 2023: 20 · 2022: 16 · 2021: 19 · 2020: 14 · 2019: 21 · 2018: 11 · 2017: 14 · 2016: 21 · 2015: 16 · 2014: 21 · 2013: 27 · 2012: 16
- FWCI
- 17.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- National Institute on Aging (R01AG022595)
- 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
- Aβ40, amyloid-beta 42, Alzheimer's disease, amyloid deposition, amyloid plaques, Tg2576 mice, bitransgenic mice, cerebrovascular amyloid
- MeSH terms
- Amyloid, Animals, Humans, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Amyloid beta-Peptides, Mice, Plaque, Amyloid
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