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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 801–900 of 1,063
Sun, X., Bhadelia, R. A., Liebson, E. S., Bergethon, P. R., Folstein, M. F., Zhu, J., Mwamburi, D. M., Patz, S., & Qiu, W. Q. (2010) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2568 · Cited by 12
“Theses changes probably precede the Ab42 aggregation and deposition in the brain that is the defining pathology of AD (Kawarabayashi et al., 2001; Schupf et al., 2008).”
BackgroundReddiar, S. B., de Veer, M., Paterson, B. M., Sepehrizadeh, T., Wai, D. C. C., Csóti, A., Panyi, G., Nicolazzo, J. A., & Norton, R. S. (2022) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.2c00614 · Cited by 12
Hashimoto, T., Ogino, K., Shin, R., Kitamoto, T., Kikuchi, T., & Shimizu, N. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2009.12.015 · Cited by 12
Reduction and the intracellular translocation of EphB2 in Tg 2576 mice and the effects of β‐amyloid
Qu, M., Jiang, J., Liu, X., Tian, Q., Chen, L., Yin, G., Liu, D., Wang, J., & Lq, Z. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12019 · Cited by 13
Anticoagulants inhibit proteolytic clearance of plasma amyloid beta
Yang, L., Bhattacharya, A., Li, Y., & Zhang, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.23718 · Cited by 12
Gao, L., Jiang, Y., Wei, S., Shang, S., Li, P., Chen, C., Dang, L., Wang, J., Huo, K., Deng, M., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180399 · Cited by 12
Serum levels and mutual correlations of amyloid β in patients with depression
Yasuda, S., Baba, H., Maeshima, H., Shimano, T., Inoue, M., Ichikawa, T., Shukuzawa, H., Suzuki, T., & Arai, H. (2019) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/ggi.13826 · Cited by 12
Reimers, D., Vallejo-Muñoz, M., Casarejos, M. J., Jiménez‐Escrig, A., Gonzalo‐Gobernado, R., & Bazán, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168697 · Cited by 12
Development and Characterization of a TAPIR-Like Mouse Monoclonal Antibody to Amyloid-β
Wang, J., Hara, H., Makifuchi, T., & Tabira, T. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14204 · Cited by 12
Reduced serum level of antibodies against amyloid β peptide is associated with aging in Tg2576 mice
Sohn, J.-H., So, J. O., Kim, H. J., Nam, E. J., Ha, H. J., Kim, Y. H., & Mook‐Jung, I. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.107 · Cited by 13
Wang, W., Lu, L., Wu, Q., & Jia, J. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160004 · Cited by 12
“Other studies have reached similar conclusions using the same experimental approaches [12].”
Allué, J. A., Sarasa, L., Izco, M., Pérez‐Grijalba, V., Fandos, N., Pascual‐Lucas, M., Ogueta, S., Pesini, P., & Sarasa, M. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160280 · Cited by 13
“Again, good agreement is found with immunohistochemical results [25].”
ResultMacyczko, J. R., Wang, N., Lü, W., Jeevaratnam, S., Shue, F., Martens, Y. A., Liu, C., Kanekiyo, T., Bu, G., & Li, Y. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230218 · Cited by 11
Townsend, M. K., Okereke, O. I., Xia, W., Yang, T., Selkoe, D. J., & Grodstein, F. (2011) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31821764ce · Cited by 11
Immunization for Alzheimer's disease
Sigurdsson, E. M., Frangione, B., & Wısnıewskı, T. (2002) · Drug Development Research · doi:10.1002/ddr.10068 · Cited by 14
“…Ji et al., 2001; Mackic et al., 1998; Maness et al., 1994; Martel et al., 1996; Poduslo et al., 1997, 1999; Shibata et al., 2000; Zlokovic et al., 1993] and the finding that plasma levels in Tg2576 APP mice decrease as brain amyloid burden increases [Kawarabayashi et al., 2001; Kuo et al., 2000].”
Comes, G., Manso, Y., Escrig, A., Fernandez-Gayol, O., Sanchis, P., Molinero, A., Giralt, M., Carrasco, J., & Hidalgo, J. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020251 · Cited by 10
“The situation is different at five months of age, since no amyloid plaques are yet present [23,24].”
BackgroundLRP1 at the crossroads of Aβ clearance and therapeutic targeting in Alzheimer’s disease
Deng, Y., Yin, H., Lu, Z., Lan, H., Liu, W., Zuo, C., Pan, N., Tian, X., & Gong, Q. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1669405 · Cited by 13
Rizoska, B., Zachrisson, O., Appelkvist, P., Boström, E., Björklund, M., Rachalski, A., Gkanatsiou, E., Kylefjord, H., Söderberg, L., Nygren, P., et al. (2024) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2024.103950 · Cited by 10
“This suggests that the diffuse amyloid plaques (primarily stained by 6E10) are mainly composed of insoluble A β 42 species (Kawarabayashi et al., 2001).”
BackgroundShoji, M. (2012) · Journal of Pharmacological Sciences · doi:10.1254/jphs.11r13fm · Cited by 10
Self-citationSex Differences in Hypothalamic Changes and the Metabolic Response of TgAPP Mice to a High Fat Diet
Freire‐Regatillo, A., Díaz-Pacheco, S., Frago, L. M., Arévalo, M., Argente, J., García‐Segura, L. M., CEBALLOS, M. L. D., & Chowen, J. A. (2022) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2022.910477 · Cited by 10
“The present work was performed in TgAPP 2576 mice because AD-like symptoms and pathology slowly progress with age, and they show behavioral abnormalities around 12 months of age, even before amyloid plaques develop (Hsiao et al., 1996; Kawarabayashi et al., 2001).”
MethodPiccarducci, R., Caselli, M. C., Zappelli, E., Ulivi, L., Daniele, S., Siciliano, G., Ceravolo, R., Mancuso, M., Baldacci, F., & Martini, C. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220216 · Cited by 10
Liang, C., Nguyen, G. A. H., Danh, T. B., Sandhu, A. K., Melkonyan, L. L., Syed, A. U., & Mukherjee, J. (2023) · Synapse · doi:10.1002/syn.22265 · Cited by 11
Nonhuman Amyloid Oligomer Epitope Reduces Alzheimer’s-Like Neuropathology in 3xTg-AD Transgenic Mice
Rasool, S., Martínez‐Coria, H., Milton, S. C. F., & Glabe, C. G. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8478-7 · Cited by 10
Soluble amyloid-β in the brain: The scarlet pimpernel
Tabaton, M., & Gambetti, P. L. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s315 · Cited by 10
Lelos, M. J., & Good, M. A. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12527 · Cited by 9
“…1992; Hsiao et al., 1995; Hsiao et al.,1996), and displays multiple features of amyloidrelated neuropathology, including age-dependent deposition of oligomeric, soluble and insoluble beta-amyloid (Ab) 1–40 and Ab 1–42 throughout cortical and subcortical brain regions (Kawarabayashi et al., 2001).”
BackgroundLain, E., Penke, B., Delacourte, A., Gündisch, D., Schröder, H., & Witter, B. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03909.x · Cited by 10
“Similar ranges have been demonstrated in plaque-forming mouse strains such as the Tg2576 mouse (Kawarabayashi et al., 2001).”
ResultRodríguez-López, A., Esteban, D., Domínguez‐Romero, A. N., & Gevorkian, G. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115189 · Cited by 9
Mishra, R., & Upadhyay, A. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05668-y · Cited by 11
Singhaarachchi, P. H., Antal, P., Calon, F., Culmsee, C., Delpech, J.-C., Feldotto, M., Geertsema, J., Hoeksema, E. E., Kőrösi, A., Layé, S., et al. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102821 · Cited by 13
Liu, P., Shang, H., Yue, C., Xu, Y., Gu, H., Wang, X., Zhou, C.-M., & Yang, J. (2022) · Chemical Engineering Journal · doi:10.1016/j.cej.2022.134657 · Cited by 9
Models of cerebral amyloid angiopathy-related intracerebral hemorrhage
Vargas-George, S. A., & Dave, K. R. (2022) · Brain Hemorrhages · doi:10.1016/j.hest.2022.05.001 · Cited by 10
Unveiling the Molecular Footprint: Proteome-Based Biomarkers for Alzheimer’s Disease
Jain, M., Dhariwal, R., Patil, N., Ojha, S., Tendulkar, R., Tendulkar, M., Dhanda, P. S., Yadav, A., & Kaushik, P. (2023) · Proteomes · doi:10.3390/proteomes11040033 · Cited by 11
PARKINSON, J. R., Ploeger, B. A., Appelkvist, P., Bogstedt, A., Bergstedt, K. D., Eketjäll, S., & Visser, S. A. G. (2013) · Pharmacology Research & Perspectives · doi:10.1002/prp2.12 · Cited by 9
“Consequently, Tg2576 mice produce highly elevated Ab levels followed by the formation of Ab plaques, as well as age-dependent behavioral, learning, and memory impairment (Hsiao et al. 1996; Chapman et al. 1999; Kawarabayashi et al. 2001; Sasaki et al. 2002; Middei et al. 2006).”
BackgroundResultMatsuda, J.-I., Kaminaka, K., & Nozaki, C. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.02.153 · Cited by 9
Savonenko, A. V., Wong, P. C., & Li, T. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85654-6.00022-8 · Cited by 8
Sex Hormones, Amyloid Protein, and Alzheimer Disease—Reply
Gandy, S. (2001) · JAMA · doi:10.1001/jama.286.7.790 · Cited by 9
Movsesyan, N., Davtyan, H., Mkrtichyan, M., Petrushina, I., Tiraturyan, T., Ross, T. M., Agadjanyan, M. G., Ghochikyan, A., & Cribbs, D. H. (2010) · Human Gene Therapy · doi:10.1089/hum.2009.219 · Cited by 9
“It has been shown that as Tg2576 animals age, Ab is altered beginning at the age of 6–7 months (Hsiao et al., 1996; Kawarabayashi et al., 2001).”
Neuropathological Verisimilitude in Animal Models of Alzheimer's Disease
Trojanowski, J. Q. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64858-4 · Cited by 8
“Although an enzyme-linked immunosorbent assay designed to measure the secreted human -secretase cleavage product (APPs swe) of APPswe did not demonstrate any abnormalities with aging in the brains of these transgenic mice, Gau and colleagues(9) did detect an age-dependent increase in soluble A 40 and A 42 levels and p…”
ResultAlcantara‐Gonzalez, D., Kennedy, M., Criscuolo, C., Botterill, J. J., & Scharfman, H. E. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01747-1 · Cited by 10
Wei, S., Dang, L., Gao, F., Wang, J., Wang, J., & Qu, Q. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220240 · Cited by 8
Kollarik, S., Moreira, C. G., Dias, I., Bimbiryte, D., Miladinovic, D., Buhmann, J. M., Baumann, C. R., & Noaín, D. (2022) · Neurodegenerative Diseases · doi:10.1159/000527786 · Cited by 9
Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease
Qin, H., Zhou, L., Haque, F. T., Martín-Jiménez, C., Trang, A., Benveniste, E. N., & Wang, Q. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.16002 · Cited by 10
“In this model, A β plaques begin to accumulate at 6 months and progress in an age-dependent manner, rendering it an ideal model for aging (Kawarabayashi et al., 2001 ).”
Elia, A., Parodi‐Rullán, R. M., Vázquez‐Torres, R., Carey, A. M., Zhao, H., Javadov, S. A., & Fossati, S. (2026) · Advanced Science · doi:10.1002/advs.202511924 · Cited by 9
“These findings align with the age dependent A β pathology in the Tg2576 mouse model, characterized by higher abundance and progressive increase in cerebral A β 40 levels compared to A β 42 [ 20 ].”
InfluentialLRRTM3 is Dispensable for Amyloid-β Production in Mice
Laakso, T., Muggalla, P., Kysenius, K., Laurén, J., Paatero, A., Huttunen, H. J., & Airaksinen, M. S. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120193 · Cited by 8
Mitchell, J. C., Perkinton, M. S., Yates, D. M., Lau, K., Rogelj, B., Miller, C. C. J., & McLoughlin, D. M. (2010) · PubMed · doi:10.3233/jad-2009-1341 · Cited by 8
Hurko, O., Boudonck, K. J., Gonzales, C., Hughes, Z. A., Jacobsen, J. S., Reinhart, P. H., & Crowther, D. (2010) · International Journal of Alzheimer s Disease · doi:10.4061/2010/864625 · Cited by 8
“[65] have previously shown that the accumulation of amyloid β plaques in the Tg2576 mouse model only reach the levels seen in AD brain between 15 and 23 months of age.”
BackgroundA Novel Form of Compensation in the Tg2576 Amyloid Mouse Model of Alzheimer’s Disease
Somogyi, A., Katonai, Z., Alpár, A., & Wolf, E. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00152 · Cited by 7
“At later stages, plaque deposition has been shown to be increasing together with the amount of soluble Aβ (Kawarabayashi et al., 2001) in these animals.”
BackgroundGnanaprakash, M., Staniszewski, A., Zhang, H., Pitstick, R., Kavanaugh, M. P., Arancio, O., & Nicholls, R. E. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-200462 · Cited by 9
“4A and B, and consistent with published reports [30, 38], we found that mice carrying the Tg2576 transgene expressed APP at 4-5 x endogenous levels.”
BackgroundA welcoming environment for amyloid plaques
Carlson, G. A. (2003) · Nature Neuroscience · doi:10.1038/nn0403-328 · Cited by 8
VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress
Wu, A., Lee, D., & Xiong, W. (2024) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2024.2392700 · Cited by 7
“Specifically, Vps35 heterozygotes in the Tg2576 transgenic mouse model of AD, which expresses human APP with Swedish mutations known to cause familial forms of the disease [72,73], expedites the AD-relevant neuropathology [29], suggesting a role of loss of VPS35/retromer for AD progression.”
Fernández‐Fernández, D., Dorner‐Ciossek, C., Kroker, K. S., & Rosenbrock, H. (2015) · Journal of Neuroscience Research · doi:10.1002/jnr.23701 · Cited by 7
“Throughout the following discussion, we will use Ab in reference to both Ab40 and Ab42 oligomers, which are gradually increased in the Tg2576 mouse during aging (Kawarabayashi et al., 2001, 2004) unless otherwise stated.”
BackgroundMethodInfluentialSerum Levels of Albumin–β-Amyloid Complex in Patients with Depression
Inoue, M., Baba, H., Yamamoto, K., Shimada, H., Yamakawa, Y., Suzuki, T., Miki, T., & Arai, H. (2016) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2016.05.005 · Cited by 7
Kollarik, S., Bimbiryte, D., Sethi, A., Dias, I., Moreira, C. G., & Noaín, D. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1519225 · Cited by 8
Gandbhir, O., & Sundaram, P. (2019) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-190107 · Cited by 7
“These observations are supported by similar studies where conjugation of peptides to PEG and HSA improved bioavailability [24].”
ResultBabušíková, E., Evinová, A., Hatok, J., Dobrota, D., & Jurecekov, J. (2013) · InTech eBooks · doi:10.5772/54619 · Cited by 8
Emmer, K. L., Covy, J. P., & Giasson, B. I. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.12.005 · Cited by 7
Hartlage‐Rübsamen, M., Ratz, V., Zeitschel, U., Finzel, L., Machner, L., Köppen, J., Schulze, A., Demuth, H., von Hörsten, S., Höfling, C., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0726-2 · Cited by 7
In Search of the Molecular Basis of Memory Loss in Alzheimer Disease
Ashe, K. H. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000213847.66742.d9 · Cited by 7
Self-citationCholinergic Neurotransmission, Amyloid-β Peptide and the Pathogenesis of Alzheimer's Disease
Liu, L. (2003) · Cited by 7
Iwata, N., Tsubuki, S., Sekiguchi, M., Watanabe-Iwata, K., Matsuba, Y., Kamano, N., Fujioka, R., Takamura, R., Watamura, N., Kakiya, N., et al. (2024) · Life Science Alliance · doi:10.26508/lsa.202402650 · Cited by 8
Self-citationAlzheimer's Disease: Focus on the Neuroprotective Role of Melatonin
Srinivasan, V., Lauterbach, E. C., Ahmed, A. H., & Prasad, A. (2012) · Journal of Neurology Research · doi:10.4021/jnr.v2i3.93 · Cited by 6
“Administration of melatonin (10 mg/kg) alleviated learning and memory deficits and also reduced the number of apoptotic neurons [43].”
BackgroundTao, Q., Zhu, H., Chen, X., Stern, R. A., Kowall, N. W., Au, R., Blusztajn, J. K., & Qiu, W. Q. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170948 · Cited by 6
van Gerresheim, E. F., Herring, A., Gremer, L., Müller‐Schiffmann, A., Keyvani, K., & Korth, C. (2020) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12685 · Cited by 6
“The amount of insoluble Aβ in tgCRND8 and in tgCRND8/tgDimer mouse brains was determined by performing a four-step ultracentrifugation as described previously (19).”
MethodSchütze, S., Döpke, A., Kellert, B., Seele, J., Ballüer, M., Bunkowski, S., Kreutzfeldt, M., Brück, W., & Nau, R. (2022) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-210049 · Cited by 7
Rodríguez-López, A., Torres-Paniagua, A. M., Acero, G., Díaz, G., & Gevorkian, G. (2023) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2023.578150 · Cited by 6
Lee, H., Perry, G. L., Zhu, X., Nunomura, A., & Smith, M. A. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.03.014 · Cited by 6
Revisiting the dilution factor as vital parameter for sensitivity of ELISA assay in CSF and Plasma
Thakur, K., Sharma, S., Prabhakar, S. K., Gupta, P., & Anand, A. (2015) · Annals of Neurosciences · doi:10.5214/ans.0972.7531.220108 · Cited by 7
Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans
Groh, N., Gallotta, I., Lechler, M. C., Huang, C., Jung, R., & David, D. C. (2017) · Journal of Visualized Experiments · doi:10.3791/56464 · Cited by 6
van der Willik, K. D., Ghanbari, M., Fani, L., Compter, A., Ruiter, R., Stricker, B. H. C., Schagen, S. B., & Ikram, M. A. (2020) · Cancer Epidemiology Biomarkers & Prevention · doi:10.1158/1055-9965.epi-20-0167 · Cited by 6
Upregulation of extracellular proteins in a mouse model of Alzheimer’s disease
Kim, S., Fuselier, J., Latoff, A., Manges, J., Jazwinski, S. M., & Zsombok, A. (2023) · Scientific Reports · doi:10.1038/s41598-023-33677-z · Cited by 5
Serum-dependent and -independent regulation of PARP2
Sun, Q., Gatie, M. I., & Kelly, G. M. (2019) · Biochemistry and Cell Biology · doi:10.1139/bcb-2018-0345 · Cited by 6
Neuroimaging in Dementia: In Vivo Amyloid Imaging
Suhara, T., Higuchi, M., & Miyoshi, M. (2008) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.215.119 · Cited by 7
“As levels of this Aβ subspecies in model mice are much lower t han those i n AD pa t i en t s (Kawarabayashi et al. 2001; Güntert et al. 2006), these findings plausibly explain the advantages of high-SA tracers in the sensitive detection of mouse amyloid, and highlight the significance of Aβ…”
BackgroundKawarabayashi, T., Terakawa, T., Takahashi, A., Hasegawa, H., Narita, S., Sato, K., Nakamura, T., Seino, Y., Hirohata, M., Baba, N., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190023 · Cited by 6
“The other half of the brain was fractionated by three sequential extraction steps using Tris-buffered saline (TBS) with protease inhibitors (Complete®, Roche Diagnostics, Basel, Switzerland), 2% sodium dodecyl sulfate (SDS) in water with the same protease inhibitors, and then 70% formic acid (FA) in water for biochemi…”
BackgroundMethodInfluentialSelf-citationZhai, T., Zhang, W., Ma, C., Ma, Y., Paulus, Y. M., Su, E. J., Murphy, G. G., Lawrence, D. A., & Wang, X. (2024) · Journal of Biomedical Optics · doi:10.1117/1.jbo.29.12.126002 · Cited by 5
“33 Bader et al. observed A β on the cerebral cortex from 5 months onward until 10 months, in 5xFAD phenotype mice.”
Höfling, C., Shehabi, E., Kuhn, P., Lichtenthaler, S. F., Hartlage‐Rübsamen, M., & Roßner, S. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00137 · Cited by 5
“These mice overexpress hAPP harboring the Swedish double mutation KM670/671NL and develop Abeta deposits starting in entorhinal cortex followed by hippocampus at around 11 months of age (Hsiao et al., 1996; Kawarabayashi et al., 2001; Hartlage-Rübsamen et al., 2011).”
BackgroundJung, C., Yamashita, H., Kato, R., Zhou, C., Matsushita, H., Takeuchi, T., Abdelhamid, M., Chen, Y., & Michikawa, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032741 · Cited by 6
“These mice have high levels of Aβ plaque deposition around 7–9 months of age [52], and they show cognitive impairment at 6-month-old age [53].”
BackgroundSawmiller, D. R., Koyama, N., Fujiwara, M., Segawa, T., Maeda, M., & Mori, T. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104846 · Cited by 5
“Brain Aβ1–40 and Aβ1–42 species were detected by a threestep extraction protocol with modifications (65).”
MethodShin, Y., Hamm, L., Murakami, S., Buirst, K., Buonarati, M., Cox, A. A., Regal, K., Hunt, K. W., Scearce-Levie, K., Watts, R., et al. (2013) · Archives of pharmacal research · doi:10.1007/s12272-013-0215-2 · Cited by 5
“In these mice, Ab peptide concentrations increase rapidly at around 6 months, coincident with the appearance of detergent-insoluble Ab (Kawarabayashi et al. 2001) and cognitive ability declines progressively thereafter (Westerman et al.”
Backgrounda prospective case-cohort study
van Oijen, M., Albert Hofman, D., Breteler, M. M. B., Koudstaal, P. J., & Soares, H. D. (2006) · Cited by 5
PET Applications in Animal Models of Neurodegenerative and Neuroinflammatory Disorders
Higuchi, M., Maeda, J., Ji, B., Tokunaga, M., Zhang, M., Maruyama, M., Ono, M., Fukumura, T., & Suhara, T. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_167 · Cited by 5
“…studies (Saido et al. 1995), followed by reports by different groups demonstrating fibrillogenic and neurotoxic propensities of this Ab subtype (He and Barrow 1999; Russo et al. 2002; Schilling et al. 2006), and biochemical assays of AD and transgenic mouse brains (Kawarabayashi et al. 2001).”
BackgroundResultKusaka, T., Ueno, M., Miki, T., Kanenishi, K., Nagai, Y., Huang, C., Okamoto, Y., Ogawa, T., Onodera, M., Itoh, S., et al. (2007) · Microscopy Research and Technique · doi:10.1002/jemt.20448 · Cited by 5
“Some researchers have demonstrated that Ab or Ablike proteins are accumulated in ischemic adult animal brains (Ishimaru et al., 1996; Popa-Wagner et al., 1998; Van Groen et al., 2005) or in aged Tg2576 transgenic mouse model of Alzheimer’s disease (Kawarabayashi et al., 2001).”
BackgroundImaging in Neurology Research II: PET Imaging of CNS Disorders
Henriksen, G., & Drzezga, A. E. (2010) · Springer eBooks · doi:10.1007/978-3-642-12945-2_33 · Cited by 5
Chandrashekar, D. V., Jagadeesan, N., Abdullah, T., Chang, R., Steinberg, R. A., Sanchez, F., Khal, E., Yang, J., Cribbs, D. H., Han, D., et al. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1526571 · Cited by 5
Fauré, L. M. P., Gauzin, S., Lejards, C., Rampon, C., & Verret, L. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.106799 · Cited by 5
Proteases in the Nervous System
Cynis, H., Lichtenthaler, S. F., Wagner, L., & Demuth, H. (2013) · Springer eBooks · doi:10.1007/978-3-7091-0885-7_10 · Cited by 4
Immunotherapy Against N-Truncated Amyloid-β Oligomers
Bayer, T. A., & Wirths, O. (2016) · Methods in pharmacology and toxicology · doi:10.1007/978-1-4939-3560-4_3 · Cited by 4
Bergamini, G., Massinet, H., Durkin, S., & Steiner, M. A. (2022) · Physiology & Behavior · doi:10.1016/j.physbeh.2022.113787 · Cited by 4
Clinical course and serum amyloid β levels in elderly patients with major depressive disorder
Natsume, S., Baba, H., Maeshima, H., Saida, T., Yoshinari, N., Shimizu, K., & Suzuki, T. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.07.073 · Cited by 5
Chapter 5.5 Transgenic mouse models of Alzheimer's disease and episodic-like memory
Borchelt, D., & Savonenko, A. V. (2008) · Handbook of behavioral neuroscience · doi:10.1016/s1569-7339(08)00230-0 · Cited by 4
Detecting Alzheimer disease before it happens
Quinn, J. F., & Sabbagh, M. N. (2008) · Neurology · doi:10.1212/01.wnl.0000316808.21277.69 · Cited by 4
Reddy, P. H., McWeeney, S. K., Park, B. S., Mańczak, M., Gutala, R. V., Jung, Y., Yau, V., Searles, R. P., Mori, M., & Joseph, Q. (2004) · Neurobiology of Aging · doi:10.1016/s0197-4580(04)80540-2 · Cited by 4
Metabolic Syndrome as a Risk Factor for Alzheimer Disease
Farooqui, A. A. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7318-3_8 · Cited by 5
What's New on Alzheimer's Disease? Insights From AD Mouse Models
Rey, C. C., Cattaud, V., Rampon, C., & Verret, L. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11400-x · Cited by 6
“The age-dependent increase of Aβ in the brain of these mice results in the establishment of extracellular amyloid plaques in the cortex and hippocampus at 10–12 months of age (Kawarabayashi et al., 2001).”
BackgroundFreitag, K., Sterczyk, N., Schulz, J., Houtman, J., Fleck, L., Sigrist, S. J., Heppner, F. L., & Jendrach, M. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.27.424477 · Cited by 4
The Role of Circulating Aβ Seeds in the Progression of Cerebral Amyloidosis
Gamez, N., & Morales, R. (2022) · Neuroscience Insights · doi:10.1177/26331055221123072 · Cited by 4
In Vivo Seeding of Amyloid-β Protein and Implications in Modeling Alzheimer’s Disease Pathology
Liu, Q., Song, S., Liu, L., & Hong, W. (2025) · Biomolecules · doi:10.3390/biom15040571 · Cited by 5
“APP23 and Tg2576 mice carry the APP Swedish mutation (K670N/M671L), which primarily enhances the cleavage efficiency of β -secretase (BACE) on APP, leading to age-related increase in total A β production and the A β 40/42 ratio [36,37,133–135].”
Latina, V., Introna, M. D., Malerba, F., Florio, R., Balzamino, B. O., Natale, G. D., Sciacca, M. F. M., Pappalardo, G., Micera, A., Pignataro, A., et al. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02022-y · Cited by 3
Age and sex dependent hippocampal neuronal hyperactivity in Alzheimer model mice
Hegnet, E., Häkli, S., Koivisto, H., Miettinen, P. O., Jin, N., Gureviciene, I., & Tanila, H. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115632 · Cited by 3
Amyloidopathy in the Eye of Alzheimer′s Disease
Zhang, X. (2011) · Journal of Addiction Research & Therapy · doi:10.4172/2155-6105.s5-005 · Cited by 3
Brunner, D., Flunkert, S., Neddens, J., Duller, S., Scopes, D. I. C., Treherne, J. M., & Hutter‐Paier, B. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.09.028 · Cited by 3
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
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