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Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease
Open accessAbstract
The accumulation of amyloid β protein (Aβ) in the Tg2576 mouse model of Alzheimer's disease (AD) was evaluated by ELISA, immunoblotting, and immunocytochemistry. Changes in Aβ begin at 6–7 months as SDS-insoluble forms of Aβ42 and Aβ40 that require formic acid for solubilization appear. From 6 to 10 months, these insoluble forms increase exponentially. As insoluble Aβ appears, SDS-soluble Aβ decreases slightly, suggesting that it may be converting to an insoluble form. Our data indicate that it is full-length unmodified Aβ that accumulates initially in Tg2576 brain. SDS-resistant Aβ oligomers and most Aβ species that are N-terminally truncated or modified develop only in older Tg2576 mice, in which they are present at levels far lower than in human AD brain. Between 6 and 10 months, when SDS-insoluble Aβ42 and Aβ40 are easily detected in every animal, histopathology is minimal because only isolated Aβ cores can be identified. By 12 months, diffuse plaques are evident. From 12 to 23 months, diffuse plaques, neuritic plaques with amyloid cores, and biochemically extracted Aβ42 and Aβ40 increase to levels like those observed in AD brains. Coincident with the marked deposition of Aβ in brain, there is a decrease in CSF Aβ and a substantial, highly significant decrease in plasma Aβ. If a similar decline occurs in human plasma, it is possible that measurement of plasma Aβ may be useful as a premorbid biomarker for AD.
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TL;DR
In Tg2576 mice, formic acid-requiring Aβ42 and Aβ40 appear at 6–7 months and rise exponentially, while SDS-soluble Aβ declines slightly; plaques become evident later. As brain Aβ deposits, CSF and plasma Aβ decline, suggesting plasma Aβ may be a premorbid biomarker if a similar decline occurs in humans.
Key findings
- Formic acid-requiring Aβ42 and Aβ40 first appeared at ~7 months and were unequivocal by 8–9 months; between 6 and 12 months they increased exponentially and continued rising from 12 to 23 months to AD-like levels. SDS-soluble Aβ decreased slightly as insoluble Aβ appeared (Spearman: Aβ42 p = 0.02; Aβ40 p = 0.003; TBS/Triton fractions decreased, p = 0.009 for TBS Aβ42, TBS Aβ40, and Triton Aβ40; p = 0.05 for Triton Aβ42).
- Histopathology lagged biochemistry: at 6–10 months only isolated cored plaques were seen despite insoluble Aβ in every animal; diffuse plaques became evident by 12 months, and from 12–23 months diffuse plaques, neuritic plaques with cores, and extracted Aβ42/Aβ40 increased to levels like those in AD brain.
- In 21–23 month Tg2576 brain, only 5% of insoluble Aβ was N-terminally truncated or modified, versus 69–85% in AD brain; N3(pE) appeared late (16–23 months), and N11(pE) was not detected in Tg2576 but was detected in AD. Tg2576 initially accumulates full-length unmodified Aβ; oligomers and most modified forms appear only in older mice and at far lower levels than in AD.
- Coincident with brain deposition, CSF Aβ42 declined (p = 0.03 in text; Fig. 7 legend reports p = 0.02) and plasma Aβ42 and Aβ40 showed highly significant decreases (p = 0.008 and p = 0.006, respectively); nontransgenic littermates showed no decline, with a slight upward trend.
Methods
- Tg2576 mice and nontransgenic littermates were killed at 1–25 months; plasma was collected in 0.1% EDTA, CSF was obtained by the Carp method, and one hemibrain was frozen while the other was fixed.
- Brain was sequentially extracted by a four-step protocol (TBS, 1% Triton X-100, 2% SDS, 70% formic acid) or a two-step protocol (2% SDS then 70% formic acid); Aβ42/Aβ40 were measured by sandwich ELISA, immunoblotting, and immunocytochemistry using domain-specific antibodies.
- CSF/plasma sample sizes were Tg2576 CSF n = 45 and plasma n = 131 across age groups; nontransgenic CSF n = 10 and plasma n = 31. AD brains were stained in parallel (seven), and Table 2 AD groups were n = 6 with substantial congophilic angiopathy and n = 9 with minimal. Analyses included Spearman rank correlation and Mann-Whitney comparisons.
Limitations
- The paper has no formal limitations section; the authors state unresolved questions: why Tg2576 deposits large amounts of Aβ40, and whether the late development and relative paucity of modified or oligomeric Aβ reflects the shorter aggregation time or fundamental human/mouse biochemical differences.
- Evident: Tg2576 resembles the AD subgroup with Aβ40 predominance and congophilic angiopathy rather than most AD; only 5% of insoluble Aβ is N-terminally modified/truncated versus 69–85% in AD, N11(pE) is absent, and the authors mention minimal neurofibrillary pathology and neuronal loss in Tg2576 brain, limiting generalizability.
- Evident: SDS versus formic acid partitioning depends on extraction protocol (e.g., 21-month Tg2576: 66.2% SDS/33.1% FA four-step vs 10.6% SDS/89.4% FA two-step; AD: 81.5%/18.2% vs 13.8%/86.2%), so soluble/insoluble percentages are method-dependent. The plasma biomarker implication is explicitly conditional (“If a similar decline occurs in human plasma”).
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88 Own result · 24 No full text of the sources · 17 Own interpretation · 5 No basis given · 4 Partly supported · 4 Own method · 3 Supported · 2 Supported so far · 2 Not checked yet · 1 Sources not found · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“In our previous study (Gravina et al., 1995), ELISAs for Ax-42 (BC-05/4G8) and Ax-40 (BA-27/4G8) showed that most of the A in AD brain is N-terminally truncated or modified.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Compared with AD, Tg2576 brain has much less A that is truncated or modified at its N terminus
What the sources say
- Supportedcites Gravina et al., 1995 source
In the analysis of AD brains (page not supplied), the paper reports that the BC-05/4G8 and BA-27/4G8 ELISAs detected substantially more Aβ than assays requiring an intact N terminus. It interprets the difference as showing that much of the Aβ ending at either Aβ42(43) or Aβ40 is N-terminally truncated or modified, and elsewhere states that most Aβ in AD brains has that characteristic. (LLM, conf=0.90)
plainn = 27- Asserted: passes — The authors put it forward as true.
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In the paper
“In the 30% in which A40 was the predominant species deposited, there was typically prominent congophilic angiopathy.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Compared with AD, Tg2576 brain has much less A that is truncated or modified at its N terminus
What the sources say
- Partly supportedcites Gravina et al., 1995 sourceExperimental — accuracy not yet measured
The Results report that Aβ40 was the major form deposited in six AD brains with substantial congophilic angiopathy. They do not establish the claimed 30% figure: those six were selected for separate analysis from a series of 27 brains, and the paper does not give a percentage of all cases in which Aβ40 predominated. (LLM, conf=0.88)
plaincorrelationaln = 27- Asserted: passes — The authors put it forward as true.
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In the paper
“and both forms continued to increase substantially from 12 to 23 months, reaching levels like those seen in the AD brain (Gravina et al., 1995).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > A that requires formic acid for extraction appears at 6-8 months in Tg2576 brain and increases with aging to a level like that seen in AD brain
What the sources say
- Partly supportedcites Gravina et al., 1995 sourceExperimental — accuracy not yet measured
The ‘Analysis of Aβ in 27 AD and 6 Plaque-free Control Brains’ section (page unavailable) measures formic-acid-requiring Aβ in AD brains, including forms ending at Aβ42(43) and Aβ40. It provides AD-brain levels as a reference, but does not study a 12-to-23-month increase or establish that the levels reached at 23 months were comparable to those in AD brain. (LLM, conf=0.86)
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The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Much of the A in AD brain is N-terminally truncated or modified (Saido et al., 1995(Saido et al., , 1996;;Hosoda et al., 1998)”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Saido et al., 1995 source
- Not checked — no full text of the sourcecites Saido et al., 1996 source
- Supportedcites Hosoda et al., 1998 source
The ELISA results (p. 4) report that N-terminally modified AβN3(pyroGlu)-42 had the highest average level among the measured Aβ species in AD frontal cortex. The Discussion (p. 6) likewise identifies it as a predominant species, supporting the claim that much of the Aβ in AD brain is N-terminally truncated or modified. (LLM, conf=0.92)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“in which they are present at levels far lower than in human AD brain.”
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
“As insoluble A appears, SDS-soluble A decreases slightly”
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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In the paper
“and a substantial, highly significant decrease in plasma A.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Our data indicate that it is full-length unmodified A that accumulates initially in Tg2576 brain.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“histopathology is minimal because only isolated A cores can be identified.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“By 12 months, diffuse plaques are evident.”
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. 45
- Probably not a substantial claim. 26
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Thus, it appears that N-terminally modified or truncated forms of A, which predominate in AD brain (Saido et al., 1995(Saido et al., , 1996;;Hosoda et al., 1998), are minor species in Tg2576 brain that only begin to appear in very old mice.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Compared with AD, Tg2576 brain has much less A that is truncated or modified at its N terminus
What the sources say
- Not checked — no full text of the sourcecites Saido et al., 1995 source
- Not checked — no full text of the sourcecites Saido et al., 1996 source
- Supportedcites Hosoda et al., 1998 source
The citation is attached to the statement that N-terminally modified or truncated Aβ forms predominate in AD brain. The Discussion (p. 6) identifies AβN3(pyroGlu)-42 and Aβx-42 as predominant species in AD frontal cortex; the statement about Tg2576 mice is the citing authors’ own conclusion, not a claim attributed to this paper. (LLM, conf=0.91)
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“In our previous examination of insoluble A in 27 AD brains (Gravina et al., 1995), A42 predominated in 70% and, in 33%, there was essentially no A40 deposited.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Compared with AD, Tg2576 brain has much less A that is truncated or modified at its N terminus
What the sources say
- Partly supportedcites Gravina et al., 1995 sourceExperimental — accuracy not yet measured
The Abstract and the discussion of the 27-brain analysis report that virtually all Aβ ended at Aβ42(43) in 9 of 27 AD brains, supporting the approximately 33% with essentially no Aβ40 deposited. The discussion says Aβ40 was the major form in six cases, but it does not establish the claimed 70% figure for Aβ42 predominance across all 27 brains. (LLM, conf=0.82)
plainn = 27- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In contrast, virtually all A terminated at A42 in the two AD brains examined (Fig. 5 K, L), as occurs in ϳ33% of AD cases (Gravina et al., 1995).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The results obtained by sandwich ELISAs are confirmed by immunoblotting
What the sources say
- Supportedcites Gravina et al., 1995 source
The Abstract reports that in 9 of 27 AD brains—approximately 33%—virtually all Aβ (96%) ended at Aβ42(43). The citation supports the frequency stated in the citing sentence; the two brains shown in Fig. 5 are the citing paper’s own observation. (LLM, conf=0.91)
plainn = 2- Asserted: passes — The authors put it forward as true.
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In the paper
“and it has been suggested that the formation of SDS stable A oligomers may be an early event in AD (Enya et al., 1999).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Supportedcites Enya et al., 1999 source
The Discussion proposes that soluble SDS-stable Aβ dimers and oligomers may increase at the very initial stage of Aβ accumulation. It also suggests that deposition of SDS-stable dimers precedes deposition of SDS-dissociable Aβ, supporting the citing sentence’s hedged description of an early event in AD. Page numbers are not provided in our copy. (LLM, conf=0.91)
hedgedconditional- 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.
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In the paper
“In most AD patients, very little A40 is deposited in the brain, but in ϳ33%, extraordinary amounts of A40 are deposited, and most of these patients show substantial amyloid angiopathy (Gravina et al., 1995).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Partly supportedcites Gravina et al., 1995 sourceExperimental — accuracy not yet measured
The Abstract and the analysis of 27 AD brains report that 9 of 27 had virtually no Aβ40, while the other 18 had increasing amounts. The paper links abundant Aβ40 with substantial angiopathy in six brains, but it does not establish that most patients deposited very little Aβ40 or that approximately 33% deposited extraordinary amounts. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
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In the paper
“From 12 to 23 months, diffuse plaques, neuritic plaques with amyloid cores, and biochemically extracted A42 and A40 increase to levels like those observed in AD brains.”
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
“SDS-resistant A oligomers and most A species that are N-terminally truncated or modified develop only in older Tg2576 mice”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“As shown in Figures 4 A-D and 5G, these oligomers are not detectable at 8 months but are definitely present by 12 months and increase substantially thereafter.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The results obtained by sandwich ELISAs are confirmed by immunoblotting
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“They increased between 7 and 10 months but, even at 10 months, only a few cores were present in each section (Fig. 2 K, L).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Cored plaques appear early in Tg2576 brain
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The relevant percent-ages in 21 month Tg2576 are 66.2% SDS versus 33.1% FA with the four-step extraction and 10.6% SDS versus 89.4% FA with the two-step procedure”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The percentage of A in SDS and FA extracts of depositing Tg2576 and AD brain is influenced by the extraction procedure
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In these nontransgenic mice, there was no suggestion of a decline in A because A42 and A40 both showed a slight upward trend in CSF (Fig. 7G,H ) and plasma (Fig. 7 I, J ) with aging.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > CSF and plasma A decline as A is deposited in the Tg2576 brain
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“SDS-insoluble 4 kDa A labeled by both BAN-50 (Fig. 4 B) and 4G8 (Fig. 4 D) appeared at 6 -8 months and increased substantially by 10 months.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The results obtained by sandwich ELISAs are confirmed by immunoblotting
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“and in AD brains, 81.5% SDS versus 18.2% FA with four-step and 13.8% SDS versus 86.2% FA with two-step extraction.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The percentage of A in SDS and FA extracts of depositing Tg2576 and AD brain is influenced by the extraction procedure
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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In the paper
“In Tg2576 and AD brains, in which there is A deposition, the relative amounts of A extracted into SDS and FA with the two methods are considerably different.A much higher percentage of total A is extracted into SDS in the four-step method.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The percentage of A in SDS and FA extracts of depositing Tg2576 and AD brain is influenced by the extraction procedure
plaindirect- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In Tg2576 brains, diffuse plaques are not observed in appreciable number until 12 months, 4 months after biochemically detectable alterations in A have begun in every animal.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
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
“and it was accompanied by a decline in CSF A40, although this decrease did not achieve significance.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > CSF and plasma A decline as A is deposited in the Tg2576 brain
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“The more sensitive sandwich ELISA assays (Fig. 1 H) were able to detect small amounts of SDS-extractable A in all systemic organs (10 -24 pmol/gm), but the amount of SDSextractable A in the brain was much larger (400 pmol/gm).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Human APP expression in Tg2576 mice is not confined to the brain
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Histochemical analysis (Fig. 6) showed that AN3-pyroglutamate (N3(pE)) appears late in Tg2576 brain, accumulating between 16 and 23 months.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > N-terminally modified As accumulate in aging Tg2576 brain
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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
“Remarkably, plasma A42 ( p ϭ 0.008) and A40 ( p ϭ 0.006) both showed highly significant decreases (Fig. 7 E, F ) that paralleled the marked accumulation of brain A and the decline in CSF A that occurred between 6 and 23 months.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > CSF and plasma A decline as A is deposited in the Tg2576 brain
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.
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It may state two separate claims as one.
- Rests on an assumption: The Tg2576 transgenic mouse model is a valid model for studying human AD Aβ deposition.
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
“This indicates that, in Tg2576 brain, only 5% of insoluble A is N-terminally truncated or modified, whereas in AD brain, the corresponding percentage is 69 -85% (Table 2).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Compared with AD, Tg2576 brain has much less A that is truncated or modified at its N terminus
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“This analysis confirmed that As terminating at both A40 and A42 accumulate in aging Tg2576 brain with A40 predominating (Figs. 2, 5 K, L).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The results obtained by sandwich ELISAs are confirmed by immunoblotting
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The definite biochemical change that occurs by 10 months in Tg2576 mice is accompanied by minimal histological evidence of A deposition, although single plaque cores can be observed in many sections.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The total amounts of A42 and A40 extracted by two-step and four-step protocols are virtually identical, although slightly more A is extracted with the four-step method.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The percentage of A in SDS and FA extracts of depositing Tg2576 and AD brain is influenced by the extraction procedure
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“As insoluble (FA-requiring) A appears at 6 -9 months, the remaining A in the brain (SDS-extracted in two-step, or TBS-and Triton-extracted in four-step) decreases slightly”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
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
“Similarly, in SDS extracts, BAN-50 labeled far more 4 kDa A in Tg2576 than in AD brains (Fig. 5A), whereas 4G8 labeled large amounts of A in both Tg2576 and AD brains (Fig. 5C).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The results obtained by sandwich ELISAs are confirmed by immunoblotting
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
“Remarkably, the unequivocal biochemical change that occurred between 6 and 10 months was accompanied by minimal immunocytochemical evidence of A deposition, although isolated, cored plaques were observed in virtually every section on careful inspection (Fig. 2).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > A that requires formic acid for extraction appears at 6-8 months in Tg2576 brain and increases with aging to a level like that seen in AD brain
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
“These early cored plaques were stained by Congo red and showed green birefringence with polarized light (data not shown).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Cored plaques appear early in Tg2576 brain
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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
“Both meningeal and parenchymal blood vessels in the brain also showed progressive A accumulation.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Cored plaques appear early in Tg2576 brain
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
“Moderate levels of transgenic human APP were present in Tg2576 heart, skin, bone, and muscle, and there was some human APP in pancreas, stomach, and large intestine (Fig. 1 D).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Human APP expression in Tg2576 mice is not confined to the brain
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
“Note that SDS-soluble A decreases transiently at 8 months, when SDS-resistant, formic acid-soluble A appears.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Our immunohistochemical and biochemical analyses show that, from 10 to 21 months, there is a rapid increase in both diffuse and cored plaques in Tg2576 brain and a coordinate marked increase in SDS-dissociable and FA-requiring A, with both the biochemical and histological changes rising to levels like those observed in human AD.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
boosteddirect- 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
“Significantly, plasma A is even higher in NOR 0304 (1400 pM A42; 5600 pM A40) than in Tg2576, but NOR 0304 mice do not develop age-dependent A deposition in brain.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > 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
“The decline for CSF A42 is significant ( p ϭ 0.02), and the declines for plasma A40 and A42 are highly significant (A42, p ϭ 0.008; A40, p ϭ 0.006; Spearman's rank correlation for the 6 -23 month age range).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
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
“After this early period, oligomers and most modified forms (e.g., forms beginning at 3pE) appear, but at levels far below those observed in AD brain.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > 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
“This analysis showed that, coincident with the marked deposition of A42 and A40 in brain, there is not only a decline in CSF A but also a substantial, highly significant decrease in plasma A42 and A40.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
boostedcorrelational- 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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It may state two separate claims as one.
- Rests on an assumption: The Tg2576 transgenic mouse model is a valid model for studying human AD Aβ deposition.
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
“From 15 to 23 months ( C-H), A deposits increase in number and size and are detected both as cored plaques labeled by both BC-05 and BA-27 and as diffuse plaques, which are selectively labeled by BC-05.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
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
“In Tg2576 mice, the APP K670N,M671L transgene is expressed at highest level in the brain, but there is also substantial expression in other organs (Fig. 1)”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The Tg2576 model is like this latter group of AD patients in that there is marked congophilic angiopathy and the deposition of a large amount of A40.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
plaincorrelational- 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
“If a similar decline occurs in human plasma, it is possible that measurement of plasma A may be useful as a premorbid biomarker for AD.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Amyloid  protein (A), the principal protein in the senile plaques of Alzheimer's disease (AD), is an ϳ4 kDa secreted polypeptide”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
What the sources say
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.
In the paper
“They report that both SDSdissociable and -insoluble forms of A accumulate in human cortex”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Funato et al., 1998
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“From studies of trisomy 21 brains (Iwatsubo et al., 1994), it is generally believed that, in human AD, A deposition begins with the formation of diffuse plaques.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Iwatsubo et al., 1994 source
hedged- 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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Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“It is well established that this mutation causes concomitant increases in secreted A42 and A40 (Cai et al., 1993;Citron et al., 1994;Scheuner et al., 1996).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
What the sources say
boosteddirect- 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.
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, in all of these genetic forms of AD, A metabolism is altered in a way that fosters A aggregation and deposition.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
plaindirect- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, Tg2576 mice develop agedependent behavioral deficits as assessed by Y maze, T maze, and Morris water maze testing (Hsiao et al., 1996;Chapman et al., 1999;Westerman et al., 2000).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
What the sources say
plaindirect- 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.
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
“Sections from seven AD brains were stained in parallel.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Transgenic mice and e xtraction.
plainn = 7- 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.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“each of these genetic forms of AD either selectively increases the extracellular concentration of A42 (Suzuki et al., 1994;Borchelt et al., 1996;Duff et al., 1996;Scheuner et al., 1996;Citron et al., 1997) or increases both A42 and A40 (Cai et al., 1993;Citron et al., 1994;Scheuner et al., 1996).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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.
In the paper
“It is well established that much of the A deposited as amyloid in AD brain is resistant to SDS extraction and requires formic acid for solubilization (Roher et al., 1993).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > A that requires formic acid for extraction appears at 6-8 months in Tg2576 brain and increases with aging to a level like that seen in AD brain
What the sources say
- Not checked — no full text of the sourcecites Roher et al., 1993 source
boosted- 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.
In the paper
“because CSF A, which has a high concentration relative to plasma A, is normally cleared into blood (Ghersi-Egea et al., 1996).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > CSF and plasma A decline as A is deposited in the Tg2576 brain
What the sources say
- Not checked — no full text of the sourcecites Ghersi-Egea et al., 1996 source
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.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Secreted A is readily detected in CSF, plasma, and in medium conditioned by a wide variety of cultured cells”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
What the sources say
plain- 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.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“It is well established that A42 declines in the CSF of patients with typical late onset AD (Motter et al., 1995;Nitsch et al., 1995;Kanai et al., 1998;Andreasen et al., 1999)”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > CSF and plasma A decline as A is deposited in the Tg2576 brain
What the sources say
boosted- 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.
Probably not a substantial claim.
In the paper
“there is good evidence that A1-42 is deposited early and selectively in senile plaques (Iwatsubo et al., 1994).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
What the sources say
- Not checked — no full text of the sourcecites Iwatsubo et al., 1994 source
boostedcorrelational- 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.
In the paper
“Synthetic A1-42 forms amyloid fibrils in vitro much more readily than A1-40 (Jarrett et al., 1993)”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
What the sources say
- Not checked — no full text of the sourcecites Jarrett et al., 1993 source
plaindirect- 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.
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
“Nontransgenic tissues were processed identically in parallel with the transgenic tissues.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Transgenic mice and e xtraction.
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.
Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Early onset Alzheimer's disease can be caused by mutations in the APP (Chartier-Harlin et al., 1991;Goate et al., 1991;Murrell et al., 1991;Mullan et al., 1992), presenilin 1 (PS1) (Sherrington et al., 1995), and presenilin 2 (PS2) (Levy-Lahad et al., 1995) genes.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Key words: Alzheimer's disease; neurodegeneration; Tg2576 transgenic animal model; amyloid  protein; cerebrospinal fluid; plasma
What the sources say
plaindirect- 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.
In the paper
“They calculate that immunodetection of A in human cortex requires 400 pmol/gm insoluble A42 (or 200 pmol/gm in hippocampus) (Funato et al., 1998).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Funato et al., 1998
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.
Probably not a substantial claim.
In the paper
“In a previous study of human plasma (Scheuner et al., 1996), we showed that the Swedish APP K670N,M671L mutation increases both A42 and A40 and that other FAD-linked APP, PS1, and PS2 mutations selectively increase A42.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Scheuner et al., 1996 source
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.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“and that its biochemical detection precedes plaque formation.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Funato et al., 1998
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.
Probably not a substantial claim.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“these modifications of A are thought to be important for amyloid deposition.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
hedgedconditional- 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.
Probably not a substantial claim.
In the paper
“We have shown recently that human plasma A42 and A40 increase with aging over age 65 and that plasma A42 and A40 are heritable traits that are increased in first degree relatives of patients with typical late onset AD (Younkin et al., 1998).”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not matchedcites Younkin et al., 1998
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- 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 matched
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
“Because it is well established that CSF A42 decreases in AD, one way to account for these negative results is to postulate that plasma A42 also declines as AD develops.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
hedgeddirect- Asserted: fails — The authors may not 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 authors may not put it forward as true. The paper’s conclusions may not depend on it.
In the paper
“that insoluble A correlates with amyloid load”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Funato et al., 1998
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.
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, in Tg2576 mice as in human subjects, plasma A is likely to be derived from both peripheral organs and brain, where A may enter the bloodstream either through the normal flow of CSF or by directly crossing CNS endothelium.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
hedgedconditional- 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.
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
“Similarly, elevated plasma A could be an excellent premorbid biomarker for AD, although it is not useful as a diagnostic marker, if it identifies those who are destined to deposit A and those who are in the early stages of deposition.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
hedgedcorrelational- 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. 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
“If this also occurs in human subjects, then declining plasma A could be a useful marker for subjects in whom there is cerebral A deposition and who are, therefore, at risk for AD.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
hedgedcorrelational- 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.
Probably not a substantial claim.
In the paper
“In that report, we suggested that cerebral A deposition in FAD occurs because of an increase in CNS A that develops as part of a generalized genetic effect that also increases plasma A.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Scheuner et al., 1996 source
hedgeddirect- 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.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Because N-terminally truncated or modified A [especially forms beginning with pyroglutamate at position 3 (3pE)] and oligomers are resistant to proteolysis (Saido et al., 1996;Kuo et al., 1998)”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
What the sources say
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.
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
“If so, then analysis of symptomatic late onset patients could miss many patients whose disease was initiated by increased A in the presymptomatic period.”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
hedgedconditional- 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.
Probably not a substantial claim. It may state two separate claims as one.
The paper relies on this without support.
The human AD brain samples used for comparison are representative of Alzheimer's disease brain pathology.
“Sections from seven AD brains were stained in parallel.”
The paper relies on this without support.
N-terminal modifications or truncations of Aβ make Aβ more insoluble in human brain.
“which are thought to make A more insoluble in human brain”
The paper relies on this without support.
The Tg2576 transgenic mouse model is a valid model for studying human AD Aβ deposition.
“To determine whether CSF and plasma A decline in Tg2576 mice as A42 and A40 are deposited in the brain, we analyzed brain (Fig. 7 A, B), CSF (Fig. 7C, D), and plasma (Fig. 7 E, F ) A42 and A40 in parallel.”
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
“Tg2576 mice exhibit elevated Aβ from 2 months old onward, plaques after 6 months old, and cognitive deficits beginning at 5 months old [32,33,34].”
From VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice (2024) · cites this paper as [32]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > Compared with AD, Tg2576 brain has much less A that is truncated or modified at its N terminus
“Tg2576 21-23 months 5 A1-42 3409 Ϯ 64 26,076 A1-40 22,667 Ϯ 440 AX-42 1379 Ϯ 38 27,318 5%”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > The results obtained by sandwich ELISAs are confirmed by immunoblotting
“4G8 (anti-A17-24), which recognizes both full-length A and A that is N-terminally truncated or modified”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > CSF and plasma A decline as A is deposited in the Tg2576 brain
“This decline in CSF A42 ( p ϭ 0.03) occurred in parallel with the marked increases in brain A42 and A40”
§ Age-Dependent Changes in Brain, CSF, and Plasma Amyloid  Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease > DISCUSSION
“The decline for CSF A42 is significant ( p ϭ 0.02)”
Citations
Cites
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659 · cited 2×
“Early onset Alzheimer’s disease can be caused by mutations in the APP (Chartier-Harlin et al., 1991; Goate et al., 1991; Murrell et al., 1991; Mullan et al., 1992), presenilin 1 (PS1) (Sherrington et al., 1995), and presenilin 2 (PS2) (Levy-Lahad et al., 1995) genes.”
BackgroundThe precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619 · cited 2×
“Amyloid b protein (Ab), the principal protein in the senile plaques of Alzheimer’s disease (AD), is an ;4 kDa secreted polypeptide that is derived from several isoforms of a large protein referred to as the amyloid b protein precursor (bAPP) (Glenner and Wong, 1984; Masters et al., 1985; Kang et al., 1987 ).”
BackgroundAmyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · cited 2×
“Amyloid b protein (Ab), the principal protein in the senile plaques of Alzheimer’s disease (AD), is an ;4 kDa secreted polypeptide that is derived from several isoforms of a large protein referred to as the amyloid b protein precursor (bAPP) (Glenner and Wong, 1984; Masters et al., 1985; Kang et al., 1987).”
BackgroundCorrelative 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 5×
“In addition, Tg2576 mice develop agedependent behavioral deficits as assessed by Y maze, T maze, and Morris water maze testing (Hsiao et al., 1996; Chapman et al., 1999; Westerman et al., 2000).”
BackgroundMethodInfluentialSelf-citationCloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051 · cited 8×
“These findings suggest that, in typical late onset AD as in early onset FAD, elevated plasma Ab may be associated with the development of AD. If so, one would expect plasma Ab to be elevated in typical late onset AD. Our initial analysis of typical AD patients ( Scheuner et al., 1996 ) showed, however, that very few A…”
BackgroundInfluentialScheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · cited 5×
“In a previous study of human plasma (Scheuner et al., 1996), we showed that the Swedish APPK670N,M671L mutation increases both Ab42 and Ab40 and that other FAD-linked APP, PS1, and PS2 mutations selectively increase Ab42.”
BackgroundResultInfluentialSelf-citationJarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022 · cited 7×
“The following antibodies to Ab were used: monoclonal, BAN-50 (anti-Ab1–16), BA-27 (anti-Ab1–40), BC-05 (anti-Ab35–43), BNT-77 (anti-Ab11–28), 4G8 (anti-Ab17–24), and 6E10 (anti-Ab1–16); polyclonal, 3160 (anti-Ab1–40), Saeko (anti-C-terminal 30 amino acids of APP) (Kawarabayashi et al., 1996), and five antibodies descr…”
BackgroundInfluentialIwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · cited 4×
“From studies of trisomy 21 brains ( Iwatsubo et al., 1994 ), it is generally believed that, in human AD, Ab deposition begins with the formation of diffuse plaques.”
BackgroundInfluentialMullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B., & Lannfelt, L. (1992) · Nature Genetics · doi:10.1038/ng0892-345 · Cited by 1,513 · cited 2×
“Early onset Alzheimer’s disease can be caused by mutations in the APP(Chartier-Harlin et al., 1991; Goate et al., 1991; Murrell et al., 1991; Mullan et al., 1992 ), presenilin 1 (PS1) (Sherrington et al., 1995), and presenilin 2 (PS2) (Levy-Lahad et al., 1995) genes.”
Background
Research works printed but not linked: 2
- Westerman, 2000, Age-dependent behavioral deficit in a transgenic mouse model of Alzheimer's disease., Soc Neurosci Abstr, 26, 1318
- Younkin, 1998, Genetic elevation of plasma amyloid β protein in typical late onset Alzheimer's disease., Soc Neurosci Abstr, 24, 263
Cited by
Sorted by citations
Items 301–400 of 1,063
Anderson, J. J., Holtz, G., Baskin, P. P., Turner, M., Rowe, B. A., Wang, B., Kounnas, M. Z., Lamb, B. T., Barten, D. M., Felsenstein, K. M., et al. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.11.015 · Cited by 93
“Although measurement of CSF Ab can be performed in Tg2576 [25] and PDAPP [26] transgenic mice which overexpress Ab, the low levels of Ab present in APP-YAC mice coupled with the small volumes of CSF that can be obtained from mice precluded our use APP-YAC mice for CSF Ab determinations.”
BackgroundAluise, C. D., Robinson, R. A. S., & Butterfield, D. A. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.07.008 · Cited by 94
Lord, A., Englund, H., Söderberg, L., Tucker, S. M., Clausen, F., Hillered, L., Gordon, M. N., Morgan, D., Lannfelt, L., Pettersson, F. E., et al. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06836.x · Cited by 92
“is even more marked with biochemical analysis compared to histological analysis [26,27].”
ResultMamikonyan, G., Necula, M., Mkrtichyan, M., Ghochikyan, A., Petrushina, I., Movsesyan, N., Mina, E. W., Kiyatkin, A. B., Glabe, C. G., Cribbs, D. H., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700088200 · Cited by 95
Petrushina, I., Ghochikyan, A., Mktrichyan, M., Mamikonyan, G., Movsesyan, N., Davtyan, H., Patel, A. J., Head, E., Cribbs, D. H., & Agadjanyan, M. G. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3201-07.2007 · Cited by 92
“Biochemical analysis of the brain tissue was processed as described previously (Kawarabayashi et al., 2001), except that cortices of right hemispheres of brains were used.”
BackgroundMethodCerebrovascular Effects of Amyloid-ß Peptides: Mechanisms and Implications for Alzheimer's Dementia
Iadecola, C. (2003) · Cellular and Molecular Neurobiology · doi:10.1023/a:1025092617651 · Cited by 92
“In these mice, as in AD, As1‐42 is most abundant in plaques, whereas As1‐40 predominates in vessels ( Kawarabayashi et al., 2001 ).”
Ibuprofen Decreases Cytokine-Induced Amyloid Beta Production in Neuronal Cells
Blasko, I., Apochal, A., Boeck, G., Hartmann, T., Grubeck‐Loebenstein, B., & Ransmayr, G. N. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0451 · Cited by 92
Cebers, G., Alexander, R., Haeberlein, S. B., Han, D., Goldwater, R., Ereshefsky, L., Olsson, T., Ye, N., Rosen, L. B., Russell, M., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160701 · Cited by 92
“This hypothesis is supported by studies in transgenic mouse models of Alzheimer’s disease [9, 16–19] and most compellingly by human genetic associations.”
The relationship between amyloid-beta and brain capillary endothelial cells in Alzheimer’s disease
Su, Q., Guo, J.-H., Zhang, Y.-L., Wang, J., & Zhang, Z.-N. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.335829 · Cited by 91
Asuni, A. A., Boutajangout, A., Scholtzova, H., Knudsen, E., Li, Y. S., Quartermain, D., Frangione, B., Wısnıewskı, T., & Sigurdsson, E. M. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05149.x · Cited by 91
“These mice show rapid increases in Ab levels at approximately 6 months of age with Ab deposition developing in the following months although extensive amyloid burden is usually not observed until the animals are well into their second year (Kawarabayashi et al., 2001).”
BackgroundShort Aβ peptides attenuate Aβ42 toxicity in vivo
Moore, B. D., Martin, J., de Mena, L., Sánchez, J., Cruz, P. E., Ceballos‐Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170600 · Cited by 89
“The tissue was sequentially extracted in protease inhibitor cocktail (Roche) containing 50 µl RIPA buffer, 2% SDS, and 5 M guanidinium/50 mM Tris-HCL (Gn-HCl), as previously described (Kawarabayashi et al., 2001).”
MethodBiophysical alterations of hippocampal pyramidal neurons in learning, ageing and Alzheimer's disease
Disterhoft, J. F., Wu, W., & Ohno, M. (2004) · Ageing Research Reviews · doi:10.1016/j.arr.2004.07.001 · Cited by 90
Luo, F. R., Rustay, N. R., Ebert, U., Hradil, V. P., Cole, T. B., Llano, D. A., Mudd, S. R., Zhang, Y., Fox, G. B., & Day, M. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.08.005 · Cited by 89
“These mice do not demonstrate significant laque pathology at 7 months of age (Callahan et al., 2001; awarabayashi et al., 2001) when they demonstrate high GU in our FDG-PET study (see supplementary materials).”
BackgroundYao, Y., Chinnici, C. M., Tang, H., Trojanowski, J. Q., Lee, V. M. ‐., & Praticò, D. (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-21 · Cited by 91
“Notably, at 8 months of age, the Tg2576 mice show elevated brain levels of soluble and insoluble Aβ as well as isoprostanes, relative to their non-transgenic littermates, but they show no evidence of any brain Aβ deposits, while following the initial onset of mature plaque-like brain deposits at about 11–12 months of…”
Fabbro, S., & Seeds, N. W. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05894.x · Cited by 89
“Actually Ab levels in normal mice were less than 1% of the minimal immunodetectable levels in human brain, and less than 0.03% of the levels seen in the Tg2576 transgenic mouse expressing a human amyloid precursor protein mutation (Kawarabayashi et al. 2001).”
BackgroundInfluentialZhuo, J., & Praticò, D. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2009.12.005 · Cited by 90
“N IH -PA Author M anuscript N IH -PA Author M anuscript N IH -PA Author M anuscript Aβ plaques deposition appears in Tg2576 mouse brain around 10-12 months of age, and accumulate to significant levels by 15 months of age (Kawarabayashi et al., 2001).”
BackgroundRodriguez-Rivera, J., Denner, L. A., & Dineley, K. T. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.08.002 · Cited by 88
Plasma β amyloid and the risk of Alzheimer's disease in Down syndrome
Coppus, A. M. W., Schuur, M., Vergeer, J., Janssens, A. C. J. W., Oostra, B. A., Verbeek, M. M., & van Duijn, C. M. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.08.007 · Cited by 88
Amyloid β Levels in Human Red Blood Cells
Kiko, T., Nakagawa, K., Satoh, A., Tsuduki, T., Furukawa, K., Arai, H., & Miyazawa, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049620 · Cited by 92
Transient enriched housing before amyloidosis onset sustains cognitive improvement in Tg2576 mice
Verret, L., Krezymon, A., Halley, H., Trouche, S. G., Zerwas, M., Lazouret, M., Lassalle, J., & Rampon, C. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.05.013 · Cited by 87
“Noticeably, the A plaque burden is low in 3.5-month-old Tg2576 and will substantially increase from his age on (Kawarabayashi et al., 2001), suggesting that his protective effect might be emphasized over time.”
BackgroundResultInfluentialGereñu, G., Martišová, E., Ferrero, H., Carracedo, M., Rantamäki, T., Ramírez, M. J., & Gil-Bea, F. J. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.01.023 · Cited by 90
Krezymon, A., Richetin, K., Halley, H., Roybon, L., Lassalle, J., Francès, B., Verret, L., & Rampon, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076497 · Cited by 99
“This remodeling became clearly visible at 12 months, an age when Tg2576 mice start forming amyloid plaques in the hippocampus and cortex [23,26] and display well described memory impairments [30].”
InfluentialImbimbo, B. P., Hutter‐Paier, B., Villetti, G., Facchinetti, F., Cenacchi, V., Volta, R., Lanzillotta, A., Pizzi, M., & Windisch, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00097.x · Cited by 87
“Ab measurements For Ab measurements, left brain hemispheres were handled as described elsewhere (Kawarabayashi et al., 2001).”
Lidocaine attenuates cognitive impairment after isoflurane anesthesia in old rats
Lin, D., Cao, L., Wang, Z., Li, J., Washington, J. M., & Zuo, Z. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.12.010 · Cited by 87
Madani, R., Poirier, R., Wolfer, D. P., Welzl, H., Groscurth, P., Lipp, H., Lu, B., Mouedden, M. E., Mercken, M. H., Nitsch, R. M., et al. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.21074 · Cited by 86
“…that the brain concentrations of Journal of Neuroscience Research DOI 10.1002/jnr human Ab are at least 102–103 times higher in those models (Mucke et al., 2000; Kawarabayashi et al., 2001; Leissring et al., 2003) than the murine Ab concentrations found in our aged NEP-deficient mouse brains.”
BackgroundInfluentialLee, J., Lau, K., Perkinton, M. S., Standen, C. L., Shemilt, S. J. A., Mercken, L., Cooper, J. D., McLoughlin, D. M., & Miller, C. C. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300503200 · Cited by 83
Best, J. D., Smith, D. W., Reilly, M., O’Donnell, R., Lewis, H. D., Ellis, S., Wilkie, N., Rosahl, T. W., Laroque, P. A., Boussiquet-Leroux, C., et al. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.114330 · Cited by 84
“Because in young plaque-free mice DEA-extracted A should equate to GnHCl-extracted A (Best et al., 2005), this dose of 3 mg/kg was chosen for chronic (3-month) dosing.”
BackgroundInfluentialKauwe, J. S. K., Jacquart, S., Chakraverty, S., Wang, J., Mayo, K., Fagan, A. M., Holtzman, D. M., Morris, J. C., & Goate, A. M. (2007) · Annals of Neurology · doi:10.1002/ana.21099 · Cited by 84
Mohri, I., Kadoyama, K., Kanekiyo, T., Sato, Y., Kagitani‐Shimono, K., Saito, Y., Suzuki, K., Kudo, T., Takeda, M., Urade, Y., et al. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000240472.43038.27 · Cited by 87
“After incubation in Dulbecco_s modified Eagle_s medium without fetal bovine serum for 6 hours, the microglia were stimulated by the addition of AA (1-40) (Peptide Institute, Osaka, Japan) for 24 hours.”
BackgroundMethodInfluentialPlasma amyloid β protein is elevated in late-onset Alzheimer disease families
Ertekin‐Taner, N., Younkin, L. H., Yager, D., Parfitt, F. C., Baker, M., Asthana, S., Hutton, M. L., Younkin, S. G., & Graff‐Radford, N. R. (2007) · Neurology · doi:10.1212/01.wnl.0000278386.00035.21 · Cited by 84
Self-citationHa, T.-Y., Chang, K.-A., Kim, J. A., Kim, H.-S., Kim, S., Chong, Y. H., & Suh, Y.-H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008840 · Cited by 73
“APPswe Tg2576 mice were obtained from Taconic Farms (Germantown, NY) and were bred by mating male mice with C57B16/SJL F1 females, as recommended by the suppliers and as described by others [33].”
BackgroundMethodNeurogenesis in mouse models of Alzheimer's disease
Chuang, T. T. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.12.008 · Cited by 88
Pomara, N., Willoughby, L. M., Sidtis, J. J., & Mehta, P. D. (2005) · American Journal of Geriatric Psychiatry · doi:10.1176/appi.ajgp.13.10.914 · Cited by 88
Serum Creatinine Levels Correlate With Plasma Amyloid β Protein
Arvanitakis, Z., Lucas, J. A., Younkin, L. H., Younkin, S. G., & Graff‐Radford, N. R. (2002) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200207000-00009 · Cited by 86
“Plasma A levels may also be significantly influenced by the A deposition that occurs in AD, as we have recently shown that plasma and CSF A decrease coordinately in the Hsiao mouse model of AD (Tg2576) as A is deposited in the brain (Kawarabayashi et al., 2001).”
BackgroundSelf-citationImbimbo, B. P., Giudice, E. D., Colavito, D., D’Arrigo, A., Carbonare, M. D., Villetti, G., Facchinetti, F., Volta, R., Pietrini, V., Baroc, M. F., et al. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.129007 · Cited by 84
“It has been shown that sequential extraction of brain homogenates using SDS and FA solubilizes most of the total amyloid pool from brains of Tg2576 mice (Kawarabayashi et al., 2001), except for some plaque core and vascular amyloid.”
BackgroundMethodInfluentialHead, E., Nukala, V. N., Fenoglio, K. A., Muggenburg, B. A., Cotman, C. W., & Sullivan, P. G. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.08.014 · Cited by 84
“However, rodents do not naturally develop some forms of neuropathology observed in human brain aging, suggesting the need for extension (Kawarabayashi et al., 2001; Oddo et al., 2003) higher mammalian model systems (Price et al., 1985; Head et al., 2001) such as the canine (Cummings et al., 1996;…”
Svedberg, M. M., Hall, H., Hellström‐Lindahl, E., Estrada, S., Guan, Z.-Z., Nordberg, A. K., & Långström, B. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2008.12.016 · Cited by 85
Plasma β-Amyloid and Cognitive Decline
Cosentino, S., Stern, Y., Sokolov, E., Scarmeas, N., Manly, J. J., Tang, M. X., Schupf, N., & Mayeux, R. P. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.189 · Cited by 84
Kreutzer, A. G., Hamza, I. L., Spencer, R. K., & Nowick, J. S. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b01332 · Cited by 85
Shemer, I., Holmgren, C. D., Min, R., Fülöp, L., Zilberter, M. Y., Sousa, K. M., Farkas, T., Härtig, W., Penke, B., Burnashev, N., et al. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04733.x · Cited by 86
“Because one-third of the total Ab load consists of soluble Ab monomers, oligomers and protofibrils (Kawarabayashi et al., 2001), their sustained 100–200 nm concentrations present in the cortices of APPswe ⁄ PS1dE9 mice are well comparable to the Ab load in tissue slices following brief Ab(25)35)ol…”
BackgroundEarly locus coeruleus degeneration and olfactory dysfunctions in Tg2576 mice
Guérin, D., Sacquet, J., Mandairon, N., Jourdan, F., & Didier, A. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.05.020 · Cited by 82
“This wellcharacterized transgenic strain develops an age-dependent elevation of Amyloid-beta protein (A) brain levels (soluble A1-40 and A1-42) with an onset at 8 months of age and with A-containing neuritic plaques occurring in the neocortex and hippocampus by 10–16 months (Hsiao et al., 1996; Jacobsen et al., 2006;…”
BackgroundInfluentialAmyloid-β Peptide and Oligomers in the Brain and Cerebrospinal Fluid of Aged Canines
Head, E., Pop, V., Sarsoza, F. M., Kayed, R., Beckett, T. L., Studzinski, C. M., Tomic, J. L., Glabe, C. G., & Murphy, M. P. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1397 · Cited by 84
Murine models of Alzheimer's disease and their use in developing immunotherapies
Wısnıewskı, T., & Sigurdsson, E. M. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.05.004 · Cited by 84
High mobility group box protein‐1 inhibits microglial Aβ clearance and enhances Aβ neurotoxicity
Takata, K., Kitamura, Y., Tsuchiya, D., Kawasaki, T., Taniguchi, T., & Shimohama, S. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20340 · Cited by 82
“The cytosolic fraction extracted by Tris-buffered saline (TBS) and the formic acid (FA) fraction extracted from the pellet by FA were prepared as described previously (Kawarabayashi et al., 2001).”
MethodAge-progressing cognitive impairments and neuropathology in transgenic CRND8 mice
Hyde, L. A., Kazdoba, T. M., Grilli, M., Lozza, G., Brussa, R., Zhang, Q., Wong, G. T., McCool, M. F., Zhang, L., Parker, E. M., et al. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.12.017 · Cited by 83
Studzinski, C. M., MacKay, W. A., Beckett, T. L., Henderson, S. T., Murphy, M. P., Sullivan, P. G., & Burnham, W. M. (2008) · Brain Research · doi:10.1016/j.brainres.2008.06.005 · Cited by 82
Amyloid-β dimers in the absence of plaque pathology impair learning and synaptic plasticity
Müller‐Schiffmann, A., Herring, A., Abdel‐Hafiz, L., Chepkova, A. N., Schäble, S., Wedel, D., Horn, A. H. C., Sticht, H., Silva, M. A. D. S., Gottmann, K., et al. (2015) · Brain · doi:10.1093/brain/awv355 · Cited by 86
Miners, J. S., Helmond, Z. V., Kehoe, P. G., & Love, S. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00375.x · Cited by 80
Klingner, M., Apelt, J., Kumar, A., Sorger, D., Sabri, O., Steinbach, J., Scheunemann, M., & Schliebs, R. (2003) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2003.08.001 · Cited by 83
Kinetics of Inhibition of β-Amyloid Aggregation by Transthyretin
Liu, L., & Murphy, R. M. (2006) · Biochemistry · doi:10.1021/bi0618520 · Cited by 80
Pyroglutamate-Aβ: Role in the natural history of Alzheimer's disease
Gunn, A. P., Masters, C. L., & Cherny, R. A. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.08.015 · Cited by 79
Sabbagh, J. J., Kinney, J. W., & Cummings, J. L. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.02.027 · Cited by 80
“CSF changes have also been assessed in animal odels of AD and show a similar trend to humans, i.e., an ncrease in phospho-tau (Zilka et al., 2010) and a reduction n Aß (Head et al., 2010; Kawarabayashi et al., 2001).”
BackgroundLee, E. B., Skovronsky, D., Abtahian, F., Doms, R. W., & Lee, V. M. ‐. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210105200 · Cited by 78
Mori, T., Koyama, N., Yokoo, T., Segawa, T., Maeda, M., Sawmiller, D. R., Tan, J., & Town, T. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.012330 · Cited by 82
“ELISA Brain Aβ1-40 and Aβ1-42 species were detected by a three-step extraction protocol with modifications (81).”
MethodMarotta, N. P., Ara, J. E., Uemura, N., Lougee, M. G., Meymand, E. S., Zhang, B., Petersson, E. J., Trojanowski, J. Q., & Lee, V. M. ‐. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01288-2 · Cited by 84
“Sandwich ELISA The concentrations of tau, Aβ 1–40 and Aβ 1–42 in the sarkosyl-insoluble fraction of human brain extractions were measured using sandwich ELISA as previously described [19], with the following combinations of capture and reporting antibodies: Tau5/BT2+HT7 for tau [20], Ban50/BA27 for Aβ 1–40, Ban50/BC05…”
MethodJarvis, C. I., Goncalves, M. B. C. V., Clarke, E. E., Dogruel, M., Kalindjian, S. B., Thomas, S. A., Maden, M., & Corcoran, J. P. T. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07426.x · Cited by 78
“We have shown that, by giving the retinoid agonists to the Tg2576 mice either intraperitoneally or orally for 3 months from 3 to 7 months of age, a period when there is a dramatic increase in Ab production (Kawarabayashi et al., 2001), this is prevented.”
BackgroundBories, C., Guitton, M. J., Julien, C., Tremblay, C., Vandal, M., Msaid, M., Koninck, Y. D., & Calon, F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046111 · Cited by 80
“[7,42], We Found a Significant Increase in Soluble and Insoluble Ab40 and Ab42 Concentrations during the Aging Process (Fig.”
BackgroundAmyloid-β42 alters apolipoprotein E solubility in brains of mice with five familial AD mutations
Youmans, K. L., Leung, S., Zhang, J., Maus, E., Baysac, K., Bu, G., Vassar, R., Yu, C., & LaDu, M. J. (2011) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2010.12.025 · Cited by 62
“…or dissected regions, or from mouse or human samples (Brecht et al., 2004; Elliott et al., 2009; Hirsch-Reinshagen et al., 2005; Kawarabayashi et al., 2004; Kawarabayashi et al., 2001; Lesne et al., 2006; Oakley et al., 2006; Sullivan et al., 2009; Zerbinatti et al., 2006; Zhao et al., 2007).”
BackgroundMethodFowler, S., Chiang, A. C. A., Savjani, R. R., Larson, M., Sherman, M. A., Schuler, D. R., Cirrito, J. R., Lesné, S., & Jankowsky, J. L. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0572-14.2014 · Cited by 80
“…long term, and if the same degree of recovery observed here can be achieved at later stages of disease when amyloid load increases exponentially (Kawarabayashi et al., 2001; Rodgers et al., 2012) and cognitive impairment becomes progressively worse (Westerman et al., 2002; Trinchese et al.,…”
BackgroundCao, J., Huang, M., Guo, L., Zhu, L., Hou, J., Zhang, L., Pero, A., Ng, S., Gaamouch, F. E., Elder, G. A., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0824-3 · Cited by 82
Wittnam, J. L., Portelius, E., Zetterberg, H., Gustavsson, M. K., Schilling, S., Koch, B. C. P., Demuth, H., Blennow, K., Wirths, O., & Bayer, T. A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.308601 · Cited by 77
Gao, L., Tian, M., Zhao, H., Xu, Q., Huang, Y. M., Si, Q., Tian, Q., Wu, Q., Hu, X., Sun, L., et al. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13432 · Cited by 76
“However, the Tg model develops plaque deposition at 9 months (Hsiao et al. 1996; Kawarabayashi et al. 2001) and cognitive impairment at 6 months (Westerman et al. 2002).”
BackgroundRangaraju, S., Raza, S. A., Pennati, A., Deng, Q., Dammer, E. B., Duong, D., Pennington, M. W., Tansey, M. G., Lah, J. J., Betarbet, R., et al. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0906-6 · Cited by 75
Rogers, K., Felsenstein, K. M., Hrdlicka, L., Tu, Z., Albayya, F., Lee, W., Hopp, S., Miller, M.-J., Spaulding, D., Yang, Z., et al. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-61 · Cited by 75
Rasool, S., Martínez‐Coria, H., Wu, J., LaFerla, F. M., & Glabe, C. G. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12305 · Cited by 74
“Briefly soluble and insoluble Aβ fractions were isolated from whole brain homogenates using a four step extraction protocol (Kawarabayashi et al. 2001).”
Bascoul-Colombo, C., Guschina, I. A., Maskrey, B. H., Good, M. A., O’Donnell, V. B., & Harwood, J. L. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.03.005 · Cited by 79
Schilling, S., Appl, T., Hoffmann, T., Cynis, H., Schulz, K., Jagla, W., Friedrich, D., Wermann, M., Buchholz, M., Heiser, U. F., et al. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05471.x · Cited by 77
“Sequential Ab extraction was performed, essentially as described (Kawarabayashi et al. 2001).”
BackgroundMethodPeng, C., Hu, J., Liu, D., Hong, X., Wu, Y., Zhu, L., & Wang, J. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.010 · Cited by 74
“In this mouse model, the Ab starts to increase at approximately 4 months of age and the increase becomes more rapid at 8 months, and the amyloid plaques appear from 12 months onward (Chauhan et al., 2005; Kawarabayashi et al., 2001); the mice also show synaptic pathology at 4 months and memory deficit at 9e10 months o…”
BackgroundMichno, W., Nyström, S., Wehrli, P. M., Lashley, T., Brinkmalm, G., Guérard, L., Syvänen, S., Sehlin, D., Kaya, I., Brinet, D., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006604 · Cited by 75
“These data are supported by previous, immunohistochemistry-based studies on plaque polymorphism in transgenic mice that demonstrated a prominent A x-40 immunoreactivity within plaque cores, whereas A x-42 was found to stain mostly the radial periphery of cored plaques as well as diffuse deposits (25, 27, 38, 41).”
ResultComparison of Aβ levels in the brain of familial and sporadic Alzheimer's disease
Hellström‐Lindahl, E., Viitanen, M. H., & Marutle, A. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2009.03.007 · Cited by 78
Lehman, E. J. H. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg322 · Cited by 85
“homogenized in 70% formic acid (150mg/ml) as previously described (38, 39).”
MethodAmelioration of the Alzheimer's Disease Phenotype by Absence of 12/15-Lipoxygenase
Yang, H., Zhuo, J., Chu, J., Chinnici, C. M., & Praticò, D. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.04.010 · Cited by 75
Wesson, D. W., & Wilson, D. A. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.08.033 · Cited by 73
“The Tg2576 mouse displays disease-related amyloid-β (Aβ) pathological progression including soluble oligomeric, soluble fibrillary, and fibrillary Aβ aggregates and the entailing cerebral neuroinflamation and neurodegeneration (Hsiao et al., 1996; Kawarabayashi et al., 2001).”
BackgroundLiskowsky, W., & Schliebs, R. (2006) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2005.11.010 · Cited by 73
“Proteolytic processing of the human APP transgene is performed by using the murine ‘‘secretase machinery’’, and levels of b-amyloid peptides increase exponentially between 9 and 21 months of age (Apelt and Schliebs, 2001; Apelt et al., 2004; Kawarabayashi et al., 2001; Kalback et al., 2002).”
MethodKoppel, J. L., Vingtdeux, V., Marambaud, P., d’Abramo, C., Jimenez, H. T., Stauber, M., Friedman, R., & Davies, P. (2013) · Molecular Medicine · doi:10.2119/molmed.2013.00140.revised · Cited by 90
Amyloid precursor protein-induced axonopathies are independent of amyloid-β peptides
Stokin, G. B., Almenar-Queralt, A., Gunawardena, S., Rodrigues, E. M., Falzone, T., Kim, J., Lillo, C., Mount, S. L., Roberts, E. A., McGowan, E., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn240 · Cited by 72
“Ab levels were determined by endspecific sandwich-ELISA as previously described (45, 82 ).”
MethodGarcı́a-Alloza, M., Subramanian, M., Thyssen, D. H., Borrelli, L. A., Fauq, A. H., Das, P., Golde, T. E., Hyman, B. T., & Bacskai, B. J. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-19 · Cited by 71
“Aβ 40 and 42 were quantified in plasma and brain samples using colorimetric human A-beta 40 and A-beta 42 ELISA kits (WAKO Chemicals USA) as previously described [ 49 ] with modifications.”
MethodPresenilin-1 adopts pathogenic conformation in normal aging and in sporadic Alzheimer’s disease
Wahlster, L., Arimon, M., Nasser‐Ghodsi, N., Post, K. L., Serrano‐Pozo, A., Uemura, K., & Berezovska, O. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1065-6 · Cited by 72
Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease
Raimundo, A., Ferreira, S., Martins, I. C., & Menezes, R. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00035 · Cited by 74
“The activity of these molecules on the brain may lead to neuronal death, particularly in AD patients, thus explaining their phenotypic profiles (Kawarabayashi et al., 2001; Dubois et al., 2016; Li and Huang, 2016; Li et al., 2016a).”
BackgroundChen, L., Yoo, S.-E., Na, R., Liu, Y., & Ran, Q. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.01.008 · Cited by 73
Massaad, C. A., Amin, S. K., Hu, L., Yuan, M., Klann, E., & Pautler, R. G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010561 · Cited by 72
“In this particular mouse model of AD, soluble Ab levels are elevated beginning at 6 months of age, well before vascular Ab deposition [42].”
BackgroundYanagisawa, D., Ibrahim, N. F., Taguchi, H., Morikawa, S., Hirao, K., Shirai, N., Sogabe, T., & Tooyama, I. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.041 · Cited by 73
Multi-Hypergraph Learning for Incomplete Multimodality Data
Liu, M., Gao, Y., Yap, P., & Shen, D. G. (2017) · IEEE Journal of Biomedical and Health Informatics · doi:10.1109/jbhi.2017.2732287 · Cited by 68
“Besides, CSF total-tau (t-tau), CSF tau hyperphosphorylated at threonine 181 (p-tau) and the decrease of CSF amyloid β (Aβ) are shown to be related to the cognitive decline in AD/MCI patients [17], [18].”
Snow, A. D., Castillo, G. M., Nguyen, B. P., Choi, P. Y., Cummings, J. A., Cam, J. A., Hu, Q., Lake, T. P., Pan, W., Kastin, A. J., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-38645-0 · Cited by 73
Peripheral cytokine release in Alzheimer patients: correlation with disease severity
Sala, G., Galimberti, G., Canevari, C., Raggi, M. E., Isella, V., Facheris, M., Appollonio, I. M., & Ferrarese, C. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00010-1 · Cited by 72
Jarosz-Griffiths, H., Whitehouse, I. J., Baybutt, H. N., Brown, D., Kellett, K. A. B., Jackson, C. D., Turner, A. J., Piccardo, P., Manson, J. C., & Hooper, N. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.278556 · Cited by 72
Roles of p75NTR in the pathogenesis of Alzheimer's disease: A novel therapeutic target
Zeng, F., Lu, J., Zhou, X., & Wang, Y. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.06.040 · Cited by 69
Plasma Aβ Levels Do Not Reflect Brain Aβ Levels
Freeman, S. H., Raju, S., Hyman, B. T., Frosch, M. P., & Irizarry, M. C. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31803d3ae4 · Cited by 69
“Biochemically, AA40 and AA42 segregate into biochemical compartments (intracellular, membrane associated, extracellular soluble, and insoluble) defined by sequential extraction procedures (5, 6).”
BackgroundIncreased amyloid β protein levels in children and adolescents with Down syndrome
Mehta, P. D., Capone, G. T., Jewell, A., & Freedland, R. L. (2007) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2006.12.010 · Cited by 72
Hong, X., Liu, J., Zhu, G., Zhuang, Y., Suo, H., Wang, P., Huang, D., Xu, J., Huang, Y., Yu, M., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt501 · Cited by 73
Lee, J., Lau, K., Perkinton, M. S., Standen, C. L., Rogelj, B., Falinska, A. M., McLoughlin, D. M., & Miller, C. C. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405602200 · Cited by 69
Ertekin‐Taner, N., Ronald, J., Feuk, L., Prince, J. A., Tucker, M., Younkin, L. H., Hella, M., Jain, S., Hackett, A. M., Scanlin, L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddi041 · Cited by 66
“Thus, PLAU may have a greater influence on secreted than on cell-associated Ab. As most brain Ab is cell-associated ( 28 ), effects on secreted Ab that are easily detected in plasma could be hard to detect in brain.”
BackgroundMethodSelf-citationEvidence for lymphatic Aβ clearance in Alzheimer's transgenic mice
Pappolla, M., Sambamurti, K., Vidal, R., Pacheco-Quinto, J., Poeggeler, B., & Matsubara, E. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.07.012 · Cited by 69
“The brain data therefore confirm all the trends seen in previous studies with this mouse model (Kawarabayashi et al., 2001).”
InfluentialShi, Y., Lu, X., Zhang, L., Shu, H., Gu, L., Wang, Z., Gao, L., Zhu, J., Zhang, H., Zhou, D., et al. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00095 · Cited by 67
Tabuchi, M., Yamaguchi, T., Iizuka, S., Imamura, S., Ikarashi, Y., & Kase, Y. (2008) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2008.12.010 · Cited by 68
Zhu, L., Zhong, M., Zhao, J., Rhee, H., Caesar, I., Knight, E. M., Volpicelli-Daley, L., Bustos, V., Netzer, W., Liu, L., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.504365 · Cited by 70
Fernández-Fernández, L., Comes, G., Bolea, I., Valente, T., Ruiz, J., Murtra, P., Ramírez, B., Anglès, N., Reguant, J., Morelló, J. R., et al. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.11.014 · Cited by 68
Defining the toxicology of aging
Sorrentino, J. A., Sanoff, H. K., & Sharpless, N. E. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.04.004 · Cited by 69
PDE9A inhibition rescues amyloid beta-induced deficits in synaptic plasticity and cognition
Kroker, K. S., Mathis, C., Marti, A., Cassel, J., Rosenbrock, H., & Dorner‐Ciossek, C. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.03.023 · Cited by 69
“These mice show increased amounts of Ab oligomers but no overt Ab plaque deposits: Ab oligomers appear already at an age of approximately 6 months whereas amyloid plaques formation only begins by the age of 10e12 months (Kawarabayashi et al., 2001, 2004).”
Disruption of neocortical histone H3 homeostasis by soluble Aβ: implications for Alzheimer's disease
Lithner, C. U., Lacor, P. N., Zhao, W.-Q., Mustafiz, T., Klein, W. L., Sweatt, J. D., & Hernandez, C. M. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.028 · Cited by 67
Metadata
- Authors
- Kawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G.
- Affiliations
- Mayo Clinic (US)
- Mayo Clinic in Florida (US)
- RIKEN (JP)
- Gunma University (JP)
- University of Minnesota (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-01-15
- Volume
- 21
- Issue
- 2
- Pages
- 372-381
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763819
- OpenAlex
- W1929267935
- Semantic Scholar
- 3ed4c46400edeece515c7a23e469e89c233699f5
- Cited by
- 1,053
- References
- 38
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 31 · 2023: 22 · 2022: 33 · 2021: 27 · 2020: 28 · 2019: 24 · 2018: 21 · 2017: 39 · 2016: 45 · 2015: 41 · 2014: 56 · 2013: 64 · 2012: 71
- FWCI
- 29.08
- 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
- National Institutes of Health
- National Institute on Aging (P01 AG015453, AG 15453)
- 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, Alzheimer's disease, amyloid oligomers, amyloid plaques, neuritic plaques, cerebrospinal fluid amyloid, biomarkers, amyloid-beta 42, Aβ40
- MeSH terms
- Aging, Alzheimer Disease, Animals, Brain, Brain Chemistry, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Formates, Humans, Immunohistochemistry, Male, Mice, Inbred C57BL, Mice, Transgenic, Organ Specificity, Sodium Dodecyl Sulfate, Immunoblotting, Biomarkers, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-27, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-27 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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