The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index; 9 of the 56 sources its claims cite were checked for support.
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.
Overview
AI snapshot
Written from the paper’s full text.
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”).
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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.
- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
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.
- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
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)
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.
- Partly supported
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.
- 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.
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 which they are present at levels far lower than in human AD brain.”
plain- 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.
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.
- 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.
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 a substantial, highly significant decrease in plasma A.”
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.
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
“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.
- 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.
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
“histopathology is minimal because only isolated A cores can be identified.”
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.
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
“By 12 months, diffuse plaques are evident.”
plain- 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. 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.
- 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.
The cited sources support only part of this claim — read each source’s verdict below.
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.
- 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.
- 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.
- 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.
- Supported
Every source the paper cites for this claim was checked and supports it.
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.
- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
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.
- 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.
- Partly supported
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 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.
- 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 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.
- 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 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 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.
- 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 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
“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.
- 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.
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 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.
- 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 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 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.
- 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 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-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.
- 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 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 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.
- Based: passes — The paper gives a reason why it holds.
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 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.
- 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.
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.
- 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 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.
- Based: passes — The paper gives a reason why it holds.
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 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.
- 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 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
“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.
- Based: passes — The paper gives a reason why it holds.
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.
- Based: passes — The paper gives a reason why it holds.
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.
- 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 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 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.
- 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 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 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.
- 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 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 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
plain- 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.
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.
- 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 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.
- 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.
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.
- 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 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
plain- 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.
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.
- 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.
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.
- 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.
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.
- 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.
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
“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.
- 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 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.
- 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 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.
- 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 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.
- 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 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.
- Based: passes — The paper gives a reason why it holds.
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.
- 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 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.
- 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.
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.
- 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.
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.
- 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
“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.
- 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 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.
- 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
“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.
- 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
“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.
- 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
“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 201–300 of 1,063
Lanz, T. A., Hosley, J. D., Adams, W. J., & Merchant, K. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.060715 · Cited by 131
“…factor to consider for the translation of the present data to clinical application is that the Tg2576 transgenic mouse produces significantly higher levels of amyloid peptides than those seen in the corresponding human tissues (Kawarabayashi et al., 2001) or the PDAPP mouse (Masliah et al., 1996).”
BackgroundCuadrado‐Tejedor, M., Vilariño, M., Cabodevilla, F., Río, J. D., Frechilla, D., & Pérez‐Mediavilla, A. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100966 · Cited by 134
Frost, J. L., Le, K. X., Cynis, H., Ekpo, E., Kleinschmidt, M., Palmour, R. M., Ervin, F. R., Snigdha, S., Cotman, C. W., Saido, T. C., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.05.005 · Cited by 135
Self-citationZhu, L., Zhong, M., Elder, G. A., Sano, M., Holtzman, D. M., Gandy, S., Cardozo, C., Haroutunian, V., Robakis, N. K., & Cai, D. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510011112 · Cited by 160
Eketjäll, S., Janson, J., Kaspersson, K., Bogstedt, A., Jeppsson, F., Fälting, J. M., Haeberlein, S. B., Kugler, A. R., Alexander, R. C., & Cebers, G. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150834 · Cited by 132
“Mice that express mutant A PP [11] show progressive A deposition, and reducing BACE1 activity yields large decreases in amyloid plaque load [12].”
BackgroundLeuzy, A., Chiotis, K., Hasselbalch, S. G., Rinne, J. O., de Mendonça, A., Otto, M., Lleó, A., Castelo-Branco, M. S., Santana, I. J., Johansson, J. J., et al. (2016) · Brain · doi:10.1093/brain/aww160 · Cited by 135
“…CSF levels of amyloid-b42 are decreased, an observation hypothesized to reflect the sequestration of brain soluble amyloid-b into insoluble plaques, with a resultant reduction in the amount of amyloidb42 available for clearance into the CSF (Kawarabayashi et al., 2001; DeMattos et al., 2002).”
BackgroundPeskind, E. R., Li, G., Shofer, J., Quinn, J. F., Kaye, J. A., Clark, C. M., Farlow, M. R., DeCarli, C., Raskind, M. A., Schellenberg, G. D., et al. (2006) · Archives of Neurology · doi:10.1001/archneur.63.7.936 · Cited by 131
Han, B. H., Zhou, M.-L., Johnson, A. W., Singh, I., Liao, F., Vellimana, A. K., Nelson, J. W., Milner, E., Cirrito, J. R., Basak, J., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414930112 · Cited by 131
Characterization of chronic low‐level proteasome inhibition on neural homeostasis
Ding, Q., Dimayuga, E. R., Martin, S. K., Bruce‐Keller, A. J., Nukala, V. N., Cuervo, A. M., & Keller, J. N. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01885.x · Cited by 131
“The amount of protein aggregation was determined as described previously (Kawarabayashi et al. 2001).”
MethodProtein misfolding in Alzheimer’s and Parkinson’s disease: genetics and molecular mechanisms
Forloni, G., Terreni, L., Bertani, I., Fogliarino, S., Invernizzi, R. W., Assini, A., Ribizzi, G., Negro, A., Calabrese, E., & Volonté, M. A. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00076-3 · Cited by 132
“This needs to be confirmed with a longitudinal study, but it is interesting that in transgenic mice expressing APP with the Swedish mutation (Tg2576) plasma levels of A 1–42 progressively declined with age and the increasing cerebral deposition of A [90].”
BackgroundZhang, J., Cao, Q., Li, S., Lu, X., Zhao, Y., Guan, J., Chen, J., Wu, Q., & Chen, G. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.06.043 · Cited by 130
Innate immunity receptor CD36 promotes cerebral amyloid angiopathy
Park, L., Zhou, J., Zhou, P., Pistick, R., Jamal, S. E., Younkin, L. H., Pierce, J. P., Arreguin, A. J., Anrather, J., Younkin, S. G., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300021110 · Cited by 132
Self-citationAlzheimer’s disease as oligomeropathy
Ono, K. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2017.08.010 · Cited by 129
Park, L., Anrather, J., Forster, C. L., Kazama, K., Carlson, G. A., & Iadecola, C. (2004) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000105800.49957.1e · Cited by 129
“As in previous studies (Hsiao et al. 1996; Kawarabayashi et al. 2001), no evidence of A deposition, assessed by the 4G8 antibody, was observed in parenchyma and blood vessels at this age (Fig.”
ResultDoes my mouse have Alzheimer's disease?
Dodart, J., Mathis, C., Bales, K. R., & Paul, S. M. (2002) · Genes Brain & Behavior · doi:10.1034/j.1601-183x.2002.10302.x · Cited by 126
“Recently, Kawarabayashi et al. (2001) showed that Tg2576 mice display detectable amounts of detergent-insoluble Ab by the age of 6–10months, prior to histological evidence of Ab deposits in the brain.”
BackgroundToyama, H., Ye, D. G., Ichise, M., Liow, J., Cai, L., Jacobowitz, D. M., Musachio, J. L., Hong, J. S., Crescenzo, M., Tipre, D. N., et al. (2005) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-005-1780-5 · Cited by 126
“Kawarabayashi et al. reported that the density of formic acid-extractable A42 and A40 in Tg2576 mice increases exponentially and substantially from 12 to 23 months, reaching levels similar to those seen in AD brain [ 23 , 26].”
BackgroundInfluentialLiver X receptor activation restores memory in aged AD mice without reducing amyloid
Vanmierlo, T., Rutten, K., Dederen, J., Bloks, V. W., van Vark-van der Zee, L. C., Kuipers, F., Kiliaan, A., Blokland, A., Sijbrands, E. J. G., Steinbusch, H., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.07.005 · Cited by 154
“Alternatively, sodium dodecyl sulfate (SDS) and formic cid soluble A fractions were detected immunochemically sing ELISA kits against human A 40 and A 42 (Invitrogen, KHB3482 and #KHB3544, Camarillo, CA, USA) after a our phase extraction (Kawarabayashi et al., 2001).”
MethodDivergent roles of GSK3 and CDK5 in APP processing
Ryder, J. W., Yuan, S., Liu, F., Li, B., Zhou, Y., & Ni, B. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.014 · Cited by 126
Arendash, G. W., Lewis, J., Leighty, R. E., McGowan, E., Cracchiolo, J. R., Hutton, M., & Garcia, M. F. (2004) · Brain Research · doi:10.1016/j.brainres.2004.02.081 · Cited by 127
Yang, T., Hong, S. Y., O’Malley, T. T., Sperling, R. A., Walsh, D. M., & Selkoe, D. J. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.11.005 · Cited by 122
“SDS-stable Ab oligomers can be detected in the brains of APP transgenic mouse models at or before the age at which deficits in learning andmemory begin to emerge [25,34,35].”
BackgroundEffects of Stress and Stress Hormones on Amyloid-β Protein and Plaque Deposition
Dong, H., & Csernansky, J. G. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1152 · Cited by 124
Blood-brain barrier leakage in Alzheimer’s disease: From discovery to clinical relevance
Nehra, G., Bauer, B., & Hartz, A. M. S. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108119 · Cited by 127
Garcia, P., Youssef, I., Utvik, J. K., Florent-Béchard, S., Barthélémy, V., Malaplate-Armand, C., Kriem, B., Stenger, C., Koziel, V., Olivier, J.-L., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4182-09.2010 · Cited by 139
“Whereas A plaques appear after 8 –9 months (Kawarabayashi et al., 2001), these mice exhibit progressive cognitive decline starting at the age of 4 months, probably reflecting synaptic pruning attributable to chronic synaptotoxic effects of A oligomers (Kawarabayashi et al., 2004; Young et al.,…”
Insulin resistance in Alzheimer's disease
Dineley, K. T., Jahrling, J. B., & Denner, L. A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.09.001 · Cited by 125
“…Aβ is believed to be responsible for the AD-related hippocampal synaptic and cognitive dysfunction that manifests at 5–6 MO (Dineley et al., 2002, 2007; Hsiao et al., 1996; Kawarabayashi et al., 2001; Lesne et al., 2006; Nenov et al., 2014; Pirttimaki et al., 2013; Taglialatela et al., 2009).”
BackgroundBiomarkers in Alzheimer's disease drug development
Cummings, J. L. (2011) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.06.004 · Cited by 122
“CSF Ab and tau have been studied in tg mouse models of AD and in non-human primates [283,284].”
BackgroundRodent Aβ Modulates the Solubility and Distribution of Amyloid Deposits in Transgenic Mice
Jankowsky, J. L., Younkin, L. H., Gonzales, V., Fadale, D. J., Slunt, H. H., Lester, H. A., Younkin, S. G., & Borchelt, D. R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611050200 · Cited by 122
Self-citationGiedraitis, V., Sundelöf, J. E., Irizarry, M. C., Gårevik, N., Hyman, B. T., Wahlund, L., Ingelsson, M., & Lannfelt, L. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.09.023 · Cited by 127
Ma, H., Lesné, S., Kotilinek, L., Steidl-Nichols, J. V., Sherman, M. A., Younkin, L. H., Younkin, S. G., Forster, C. L., Sergeant, N., Delacourte, A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609521104 · Cited by 121
Self-citationChen, L., Na, R., Gu, M., Richardson, A. G., & Ran, Q. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05603.x · Cited by 120
“The SDS soluble and SDS insoluble Ab peptides were extracted using a protocol described by Kawarabayashi et al. (2001).”
MethodBezzina, C., Verret, L., Juan, C., Remaud, J., Halley, H., Rampon, C., & Dahan, L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119910 · Cited by 121
Excitatory-inhibitory imbalance in Alzheimer's disease and therapeutic significance
Varela, E. V., Etter, G., & Williams, S. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.04.010 · Cited by 122
Cynis, H., Scheel, E., Saido, T. C., Schilling, S., & Demuth, H. (2008) · Biochemistry · doi:10.1021/bi800250p · Cited by 117
Self-citationEssa, M. M., Subash, S., Akbar, M. D., Al‐Adawi, S., & Guillemin, G. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120964 · Cited by 118
Impact of peripheral myeloid cells on amyloid-β pathology in Alzheimer’s disease–like mice
Prokop, S., Miller, K. R., Drost, N., Handrick, S., Mathur, V., Luo, J., Wegner, A., Wyss-Coray, T., & Heppner, F. L. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20150479 · Cited by 116
Inhibition of amyloid-β plaque formation by α-synuclein
Bachhuber, T., Katzmarski, N., McCarter, J. F., Loreth, D., Tahirović, S., Kamp, F., Abou‐Ajram, C., Nuscher, B., Serrano‐Pozo, A., Müller, A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3885 · Cited by 120
Chiu, C., Miller, M. C., Caralopoulos, I. N., Worden, M. S., Brinker, T., Gordon, Z. N., Johanson, C. E., & Silverberg, G. D. (2012) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-9-3 · Cited by 116
Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model
Freitag, K., Sterczyk, N., Wendlinger, S., Obermayer, B., Schulz, J., Farztdinov, V. M., Mülleder, M., Ralser, M., Houtman, J., Fleck, L., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02534-7 · Cited by 125
Normal induction but accelerated decay of LTP in APP + PS1 transgenic mice
Gureviciene, I., Ikonen, S., Gurevicius, K., Sarkaki, A., Groen, T. V., Pussinen, R., Ylinen, A., & Tanila, H. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.11.011 · Cited by 118
“Transgenic mice carrying these mutations show an agedependent increase in the Ah levels (Kawarabayashi et al., 2001) and in many cases also an age-dependent memory impairment (Chen et al., 2000; Hsiao et al., 1996; Koistinaho et al., 2001; Puoliväli et al., 2002; Westerman et al., 2002).”
BackgroundEADI consortium, G. C., Lambert, J.-C., Grenier-Boley, B., Harold, D., Zelenika, D., Chouraki, V, Kamatani, Y., Sleegers, K., Ikram, M. A., Hiltunen, M., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.14 · Cited by 129
Sutcliffe, J. G., Hedlund, P. B., Thomas, E. A., Bloom, F. E., & Hilbush, B. S. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22603 · Cited by 105
“The plasma fraction was removed and stored at –808C. Brains were removed, frozen rapidly on dry ice, and stored at –808C. Oligomeric Ab was extracted in the SDS fraction essentially as described by Kawarabayashi et al. (2001).”
MethodShi, J., Wang, B., Tian, Y., Xu, J. L., Gao, L., Zhao, S., Jiang, T., Xie, H., & Zhang, Y. (2013) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12144 · Cited by 117
Insights into the mechanisms of action of anti‐Aβ antibodies in Alzheimer's disease mouse models
Levites, Y., Smithson, L. A., Price, R. W., Dakin, R. S., Yuan, B., Sierks, M. R., Kim, J., McGowan, E., Kim Reed, D., Rosenberry, T. L., et al. (2006) · The FASEB Journal · doi:10.1096/fj.06-6463fje · Cited by 113
“brain is 10 nmol (equivalent to the A turned over in the brain in 40 d) (58).”
BackgroundPlaques, Tangles, and Memory Loss in Mouse Models of Neurodegeneration
Eriksen, J. L., & Janus, C. G. (2007) · Behavior Genetics · doi:10.1007/s10519-006-9118-z · Cited by 146
FAD mutant PS-1 gene-targeted mice: increased Aβ42 and Aβ deposition without APP overproduction
Flood, D. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00330-x · Cited by 131
Overlapping profiles of Aβ peptides in the Alzheimer's disease and pathological aging brains
Moore, B. D., Chakrabarty, P., Levites, Y., Kukar, T. L., Baine, A.-M. T., Moroni, T., Ladd, T. B., Das, P., Dickson, D. W., & Golde, T. E. (2012) · Alzheimer s Research & Therapy · doi:10.1186/alzrt121 · Cited by 115
Lalonde, R., Lewis, T. L., Strazielle, C., Kim, H., & Fukuchi, K.-I. (2003) · Brain Research · doi:10.1016/s0006-8993(03)02694-5 · Cited by 113
Plasma β Amyloid and the Risk of Alzheimer Disease and Dementia in Elderly Men
Sundelöf, J. E., Giedraitis, V., Irizarry, M. C., Sundström, J., Ingelsson, E., Rönnemaa, E., Ärnlöv, J., Gunnarsson, M. D., Hyman, B. T., Basun, H., et al. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.57 · Cited by 113
Bell, K. A., O’Riordan, K. J., Sweatt, J. D., & Dineley, K. T. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02722.x · Cited by 117
“Tg2576 mice contain a transgene for a mutant form of human amyloid precursor protein (APP) that leads to over-production of Ab from birth (Hsiao et al. 1996; Kawarabayashi et al. 2001).”
BackgroundGlu11 Site Cleavage and N-Terminally Truncated Aβ Production upon BACE Overexpression
Liu, K., Doms, R. W., & Lee, V. M.-Y. (2002) · Biochemistry · doi:10.1021/bi015800g · Cited by 96
Hong, S., Quintero-Monzon, O., Ostaszewski, B. L., Podlisny, D. R., Cavanaugh, W. T., Yang, T., Holtzman, D. M., Cirrito, J. R., & Selkoe, D. J. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3272-11.2011 · Cited by 111
“As reported previously for the J20 line and other APP tg mice (Johnson-Wood et al., 1997; Hsia et al., 1999; Mucke et al., 2000; Kawarabayashi et al., 2001; Shankar et al., 2009), we observed an age-dependent rise in levels of all three pools of parenchymal A (Fig.”
BackgroundThakker, D. R., Weatherspoon, M. R., Harrison, J., Keene, T. E., Lane, D. S., Kaemmerer, W. F., Stewart, G. R., & Shafer, L. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813404106 · Cited by 124
“In addition to developing several other manifestations similar to AD (41, 42), Tg2576 mice represent one of the well characterized models for an age-dependent progression of CAA, exhibiting a robust vascular pathology at 16 months of age (43, 44).”
BackgroundPlasma levels of beta-amyloid (1–42) in Alzheimer's disease and mild cognitive impairment
Pesaresi, M., Lovati, C., Bertora, P., Mailland, E., Galimberti, D., Scarpini, E. A., Quadri, P., Forloni, G., & Mariani, C. B. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.03.004 · Cited by 111
ADDLs and the signaling web that leads to Alzheimer’s disease
Krafft, G. A., & Klein, W. L. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.07.012 · Cited by 113
“These deficits coincided much more closely with synaptic loss (Hsia et al., 1999; Kawarabayashi et al., 2001; Mucke et al., 2000), a process not linked to plaques or Ab deposition.”
BackgroundShibuya, Y., Chang, C. C. Y., Huang, L.-H., Bryleva, E. Y., & Chang, T.-Y. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2567-14.2014 · Cited by 108
“Brain extracts were prepared as described previously (Kawarabayashi et al., 2001).”
MethodPEDERSEN, W., & FLYNN, E. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.08.003 · Cited by 108
The role of amyloid β in the pathogenesis of Alzheimer's disease
Gilbert, B. J. (2013) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2013-201515 · Cited by 109
β‐Secretase inhibitor GRL‐8234 rescues age‐related cognitive decline in APP transgenic mice
Chang, W., Huang, X., Downs, D., Cirrito, J. R., Koelsch, G., Holtzman, D. M., Ghosh, A. K., & Tang, J. (2010) · The FASEB Journal · doi:10.1096/fj.10-167213 · Cited by 110
Jung, B.-K., Pyo, K., Shin, K. Y., Hwang, Y. S., Lim, H., Lee, S. J., Moon, J.-H., Lee, S. H., Suh, Y., Chai, J.-Y., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033312 · Cited by 108
“were obtained from Taconic (German Town, NY, USA) and were bred by mating male mice with (C57BL6/SJL) F1 females as recommended by suppliers and as described by others”
MethodAmyloid‐β oligomers impair fear conditioned memory in a calcineurin‐dependent fashion in mice
Dineley, K. T., Kayed, R., Neugebauer, V., Fu, Y., Zhang, W., Reese, L. C., & Taglialatela, G. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22445 · Cited by 110
“At this age, cognitive function is rapidly deteriorating, and initial plaque deposition may be observed (Kawarabayashi et al., 2001).”
BackgroundMicroglial transplantation increases amyloid‐β clearance in Alzheimer model rats
Takata, K., Kitamura, Y., Yanagisawa, D., Morikawa, S., Morita, M., Inubushi, T., Tsuchiya, D., Chishiro, S., Saeki, M., Taniguchi, T., et al. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.01.009 · Cited by 106
“In brief, hippocampi on the Ab-injected side were dissected and then the cytosolic fraction was extracted by 500 ll of tris-buffered saline (TBS) and the formic acid (FA) fraction extracted from the pellet by 500 ll of FA was prepared as described previously [10].”
MethodPhilipson, O., Hammarström, P., Nilsson, K. P. R., Portelius, E., Olofsson, T., Ingelsson, M., Hyman, B. T., Blennow, K., Lannfelt, L., Kalimo, H., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.11.022 · Cited by 108
Aβ1-42 stimulates actin polymerization in hippocampal neurons through Rac1 and Cdc42 Rho GTPases
Mendoza‐Naranjo, A., González-Billault, C. E., & Maccioni, R. B. (2007) · Journal of Cell Science · doi:10.1242/jcs.03323 · Cited by 110
“Such A concentrations have been detected in brain tissues of AD patients and mice transfected with human amyloid precursor protein gene (Kuo et al., 1999; McLean et al., 1999; Kawarabayashi et al., 2001; Funato et al., 1998), and are pathophysiologically relevant.”
BackgroundIn vivo inhibition of Aβ production by memapsin 2 (β‐secretase) inhibitors
Chang, W., Koelsch, G., Wong, S., Downs, D., Da, H., Weerasena, V., Gordon, B., Devasamudram, T., Bilcer, G. M., Ghosh, A. K., et al. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02452.x · Cited by 105
“It has been established previously that Ab in young Tg2576 AD mice is expressed almost entirely in the brain (Kawarabayashi et al. 2001).”
BackgroundDistinct Pools of β-Amyloid in Alzheimer Disease–Affected Brain: A Clinicopathologic Study
Steinerman, J. R., Irizarry, M., Scarmeas, N., Raju, S., Brandt, J., Albert, M., Blacker, D., Hyman, B., & Stern, Y. (2008) · Archives of Neurology · doi:10.1001/archneur.65.7.906 · Cited by 104
“5) [8-20] No.”
Specific Uptake of an Amyloid-β Protofibril-Binding Antibody-Tracer in AβPP Transgenic Mouse Brain
Magnusson, K., Sehlin, D., Syvänen, S., Svedberg, M. M., Philipson, O., Söderberg, L., Tegerstedt, K., Holmquist, M., Gellerfors, P., Максимилианович, Т. В., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130029 · Cited by 107
“The tg-ArcSwe model differs from more commonly used models like tg-Swe or Tg2576 in terms of onset of amyloid deposition, as well as plaque structure and SDS-solubility [23, 39].”
Effects of neural stem cell transplantation in Alzheimer’s disease models
Hayashi, Y., Lin, H.-T., Lee, C.-C., & Tsai, K. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-0622-x · Cited by 106
“Mice show no neurofibrillary tangles or significant neuronal loss, but they display progressive pathological protein accumulation and behavioural impairment in many studies, thus partially satisfying the requirements of a typical AD mouse model [6, 48, 49].”
BackgroundSankaranarayanan, S., Price, E. A., Wu, G., Crouthamel, M., Shi, X., Tugusheva, K., Tyler, K. X., Kahana, J. A., Ellis, J. D., Jin, L., et al. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.130039 · Cited by 101
“These mice show APP expression and A levels that are 2 to 3-fold above endogenous murine levels, and they display no amyloid plaques with age (Lamb et al., 1993) compared with other mutant-APP transgenic mice driven by strong promoter elements (Kawarabayashi et al., 2001).”
BackgroundPlasma levels of amyloid β-protein 42 are increased in women with mild cognitive impairment
Assini, A., Cammarata, S., Vitali, A., Colucci, M. E. W., Giliberto, L., Borghi, R., Inglese, M. L., Volpe, S., Ratto, S., Dagna-Bricarelli, F., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000137040.64252.ed · Cited by 104
Ishii, M., Wang, G., Racchumi, G., Dyke, J. P., & Iadecola, C. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.0872-14.2014 · Cited by 109
“Consistent with previous reports (Kawarabayashi et al., 2001), Tg2576 mice had no visible plaques at 3 months of age, sporadic small plaques at 7 months of age, and widespread, markedly larger amyloid plaques by 14 months of age (Fig.”
BackgroundMethodResultSchütt, T., Helboe, L., Pedersen, L. Ø., Waldemar, G., Berendt, M., & Pedersen, J. T. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151085 · Cited by 105
Metabolism of amyloid β peptide and pathogenesis of Alzheimer's disease
Saido, T. C., & Iwata, N. (2006) · Neuroscience Research · doi:10.1016/j.neures.2005.12.015 · Cited by 102
Self-citationPirttimaki, T. M., Codadu, N. K., Awni, A., Pratik, P., Nagel, D. A., Hill, E. J., Dineley, K. T., & Parri, H. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081828 · Cited by 103
“Importantly our study shows that Aβ1-42 levels are elevated in the first two postnatal weeks, long before synaptic and cognitive deficits can be detected [13,36,37] at 5-6 months and coincide with insoluble Aβ1-42 deposition [48,49].”
BackgroundAlexandru, A., Jagla, W., Graubner, S., Becker, A., Bäuscher, C., Kohlmann, S., Sedlmeier, R., Raber, K. A., Cynis, H., Rönicke, R., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1794-11.2011 · Cited by 102
“Furthermore, most of the mouse models of AD do not show an accumulation of N-terminally cleaved A species (Kawarabayashi et al., 2001; Kalback et al., 2002).”
BackgroundHigaki, S., Muramatsu, M., Matsuda, A., Matsumoto, K., Satoh, J., Michikawa, M., & Niida, S. (2018) · PLoS ONE · doi:10.1371/journal.pone.0196929 · Cited by 103
PET Amyloid Ligand [11C]PIB Uptake and Cerebrospinal Fluid β-Amyloid in Mild Cognitive Impairment
Koivunen, J., Pirttilä, T., Kemppainen, N. M., Aalto, S., Herukka, S., Jauhianen, A. M., Hänninen, T., Hallikainen, M., Någren, K., Rinne, J. O., et al. (2008) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000163927 · Cited by 103
“Even in non-demented individuals, a decrease in Aβ42 reflected increasing plaque load. Also, studies in transgenic mice carrying APP mutations have shown that CSF Aβ42 levels start to decrease concomitantly with the accumulation of amyloid in the brain [”
BackgroundHamaguchi, T., Eisele, Y. S., Varvel, N. H., Lamb, B. T., Walker, L. C., & Jucker, M. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0912-1 · Cited by 105
Zhang, J., Xing, J., Wang, L., Jiang, H., Guo, S., & Liu, R. (2017) · Molecules · doi:10.3390/molecules22030334 · Cited by 103
“Given that in plasma, increased levels of free Aβ were identified in AD patients as well as in AD mouse models [40,41], the accumulation of Aβ peptides is believed to be a causative event in cerebrovascular alterations [42].”
BackgroundMori, T., Koyama, N., Tan, J., Segawa, T., Maeda, M., & Town, T. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004280 · Cited by 103
Chemical sensing platforms for detecting trace-level Alzheimer's core biomarkers
Kim, K., Lee, C. H., & Park, C. B. (2020) · Chemical Society Reviews · doi:10.1039/d0cs00107d · Cited by 101
Oikawa, N., Kimura, N., & Yanagisawa, K. (2009) · Brain Research · doi:10.1016/j.brainres.2009.12.005 · Cited by 101
A Role for P-Glycoprotein in Clearance of Alzheimer Amyloid ? -Peptide from the Brain
Wang, W., M. Bodles-Brakhop, A., & W. Barger, S. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160314151012 · Cited by 107
Using Pittsburgh Compound B for In Vivo PET Imaging of Fibrillar Amyloid-Beta
Cohen, A. D., Rabinovici, G. D., Mathis, C. A., Jagust, W. J., Klunk, W. E., & Ikonomović, M. D. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00002-7 · Cited by 103
“Based on a study in Tg2576 mice (Kawarabayashi et al., 2001) it has been assumed that lower CSF Aβ42 reflects deposition of fibrillar Aβ in brain tissues; however, no direct evidence from human studies is available to confirm this hypothesis and alternate hypotheses for lowered CSF Aβ such as…”
Hu, Y., Li, C., & Shen, W. (2014) · Neuropathology · doi:10.1111/neup.12115 · Cited by 98
Chiu, K., Chan, T. F., Wu, A., Leung, I. Y.-P., So, K., & Chang, R. C. (2011) · AGE · doi:10.1007/s11357-011-9260-2 · Cited by 100
“King et al. 1999; Morgan et al. 2000; Kawarabayashi et al. 2001; Westerman et al. 2002; Duyckaerts et al. 2008”
BackgroundBest, J. D., Jay, M. T., Otu, F., Ma, J., Nadin, A. J., Ellis, S., Lewis, H. D., Pattison, C., Reilly, M., Harrison, T., et al. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.104.081174 · Cited by 98
“A number of studies have investigated the concentrations of A peptide obtained from brain following different extraction methods in transgenic mice and human post-mortem tissue (Wang et al., 1999; Kawarabayashi et al., 2001; Lewis et al., 2004).”
BackgroundKurata, T., Miyazaki, K., Kozuki, M., Panin, V.-L., Morimoto, N., Ohta, Y., Nagai, M., Ikeda, Y., Matsuura, T., & Abe, K. (2011) · Brain Research · doi:10.1016/j.brainres.2010.11.067 · Cited by 98
“…month; MC, methylcellulose; NFTs, neurofibrillary tangles; pτDN, ho, total cholesterol; Tg, transgenic; TG, triglyceride . thebrainhad substantialAβamyloiddeposits (Hsiao et al., 1996; Kawarabayashi et al., 2001) with memory disturbance and subsequent typical pathological characteristics of AD.”
BackgroundAn Update of Animal Models of Alzheimer Disease with a Reevaluation of Plaque Depositions
Lee, J. E., & Han, P. (2013) · Experimental Neurobiology · doi:10.5607/en.2013.22.2.84 · Cited by 101
“Plaque deposition levels for each line was reassessed using both the Tg2676 panels and Tg-APPswe/PS1dE9 panels [44], and plaque scores were averaged [25, 27, 44, 45, 47, 55-61].”
BackgroundMethodJacobsen, H., Ozmen, L., Caruso, A., Narquizian, R., Hilpert, H., Jacobsen, B., Terwel, D., Tanghe, A., & Bohrmann, B. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1405-14.2014 · Cited by 96
“This could be a feature of this mouse model because soluble A , as a distinct fraction of total A , was reported for other models (Kawarabayashi et al., 2001; Westerman et al., 2002).”
ResultSimmons, D. A., Knowles, J. K., Belichenko, N. P., Banerjee, G., Finkle, C., Massa, S. M., & Longo, F. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0102136 · Cited by 97
“Insoluble Ab levels incrementally increase beginning at 6 months of age [37] and Ab deposition is evident at 11 months [22,38].”
BackgroundReelin protects against amyloid β toxicity in vivo
Lane-Donovan, C., Philips, G. T., Wasser, C. R., Durakoglugil, M. S., Masiulis, I., Upadhaya, A., Pohlkamp, T., Coskun, C., Kotti, T., Steller, L., et al. (2015) · Science Signaling · doi:10.1126/scisignal.aaa6674 · Cited by 96
Seppälä, T. T., Herukka, S., Hänninen, T., Tervo, S., Hallikainen, M., Soininen, H. S., & Pirttilä, T. (2010) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2010.205757 · Cited by 98
“Aβ is present in plasma, but it is still unknown whether it originates from peripheral sources or from the brain. In Tg2576 transgenic mouse, plasma Aβ levels decline in parallel with their increasing accumulation in the brain.”
Animal models of amyloid‐β‐related pathologies in Alzheimer’s disease
Philipson, O., Lord, A., Gumucio, A., O'Callaghan, P. W., Lannfelt, L., & Nilsson, L. N. G. (2010) · FEBS Journal · doi:10.1111/j.1742-4658.2010.07564.x · Cited by 101
Mechanisms of amyloid plaque pathogenesis
Fiala, J. C. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0284-8 · Cited by 99
Ghosh, A. K., Kumaragurubaran, N., Lin, H., Kulkarni, S. S., Xu, X., Miller, H. B., Reddy, D. S., Weerasena, V., Turner, R. T., Chang, W., et al. (2007) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.12.028 · Cited by 96
Disruption of blood-brain barrier in Alzheimer disease pathogenesis
Kook, S. Y., Hong, H., Moon, M., & Mook‐Jung, I. (2013) · Tissue Barriers · doi:10.4161/tisb.23993 · Cited by 101
Liu, R., Groen, T. V., Katre, A. K., Cao, D., Kadisha, I., Ballinger, C. A., Wang, L., Carroll, S. L., & Li, L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.06.003 · Cited by 97
“For the measurement of soluble and insoluble A , ouse brain tissues were prepared according to the method escribed before (Kawarabayashi et al., 2001).”
MethodMorihara, T., Teter, B., Yang, F., Lim, G. P., Boudinot, S. G., Boudinot, F. D., Frautschy, S. A., & Cole, G. M. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300668 · Cited by 96
“Our data showed mACT mRNA was elevated in Tg2576 mice compared to non-Tg mice by 2.8-fold at 22 months of age and by 1.4-fold at 16 months, even though Ab levels are as high in these mice as those of late stage AD patients (Kawarabayashi et al, 2001).”
BackgroundInfluentialRibes, D., Colomina, M. T., Vicens, P., & Domingo, J. L. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.08.017 · Cited by 95
Epilepsy, amyloid-β, and D1 dopamine receptors: a possible pathogenetic link?
Costa, C., Parnetti, L., D'Amelio, M., Tozzi, A., Tantucci, M., Romigi, A., Siliquini, S., Cavallucci, V., Di Filippo, M., Mazzocchetti, P., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.025 · Cited by 94
Liu, K., Solano, I., Mann, D. M. A., Lemere, C. A., Mercken, M. H., Trojanowski, J. Q., & Lee, V. M. ‐. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0077-5 · Cited by 96
“To detect the more soluble A species that are thought to be the Wrst biochemical changes of A before it is deposited as SPs [18], we sequentially extracted DS brain samples using buVers of increased extraction strength and A 1-40, A 1-42 as well as A 11-40 and A 11-42 present in the samples were then separated using a…”
Method
Metadata
- Authors
- Kawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G.
- Affiliations
- Mayo Clinic (US)
- Mayo Clinic in Florida (US)
- RIKEN (JP)
- Gunma University (JP)
- University of Minnesota (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-01-15
- Volume
- 21
- Issue
- 2
- Pages
- 372-381
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763819
- OpenAlex
- W1929267935
- Semantic Scholar
- 3ed4c46400edeece515c7a23e469e89c233699f5
- Cited by
- 1,053
- References
- 38
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 31 · 2023: 22 · 2022: 33 · 2021: 27 · 2020: 28 · 2019: 24 · 2018: 21 · 2017: 39 · 2016: 45 · 2015: 41 · 2014: 56 · 2013: 64 · 2012: 71
- FWCI
- 29.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P01 AG015453, AG 15453)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta, Alzheimer's disease, amyloid oligomers, amyloid plaques, neuritic plaques, cerebrospinal fluid amyloid, biomarkers, amyloid-beta 42, Aβ40
- MeSH terms
- Aging, Alzheimer Disease, Animals, Brain, Brain Chemistry, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Formates, Humans, Immunohistochemistry, Male, Mice, Inbred C57BL, Mice, Transgenic, Organ Specificity, Sodium Dodecyl Sulfate, Immunoblotting, Biomarkers, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-27, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-27 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
