The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index; 12 of the 34 sources its claims cite were checked for support.
BRI2 (ITM2b) Inhibits A Deposition In Vivo
Open accessAbstract
Analyses of the biologic effects of mutations in the BRI2 (ITM2b) and the amyloid beta precursor protein (APP) genes support the hypothesis that cerebral accumulation of amyloidogenic peptides in familial British and familial Danish dementias and Alzheimer's disease (AD) is associated with neurodegeneration. We have used somatic brain transgenic technology to express the BRI2 and BRI2-Abeta1-40 transgenes in APP mouse models. Expression of BRI2-Abeta1-40 mimics the suppressive effect previously observed using conventional transgenic methods, further validating the somatic brain transgenic methodology. Unexpectedly, we also find that expression of wild-type human BRI2 reduces cerebral Abeta deposition in an AD mouse model. Additional data indicate that the 23 aa peptide, Bri23, released from BRI2 by normal processing, is present in human CSF, inhibits Abeta aggregation in vitro and mediates its anti-amyloidogenic effect in vivo. These studies demonstrate that BRI2 is a novel mediator of Abeta deposition in vivo.
Overview
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Written from the paper’s full text.
TL;DR
Using somatic brain transgenesis in APP mouse models, the authors show that wild-type BRI2, like BRI2-Aβ1-40, reduces cerebral Aβ deposition without altering APP processing or inducing anti-Aβ antibodies. The effect is mediated by the secreted Bri2-23 peptide, which is present in human CSF and inhibits Aβ1-42 aggregation in vitro.
Key findings
- rAAV1-delivered BRI2-Aβ1-40 suppressed parenchymal Aβ1-40 and Aβ1-42 accumulation in TgCRND8 mice, validating the somatic brain transgenic method; unexpectedly, wild-type human BRI2 also reduced Aβ deposition to an equivalent extent.
- BRI2del244-266, which lacks the Bri2-23 peptide, had no significant effect on Aβ loads, indicating the Bri2-23 sequence is required for the anti-amyloidogenic effect in vivo.
- Bri2-23 inhibited Aβ1-42 aggregation in vitro; after 120–200 h, it inhibited aggregation by 46 ± 9% (n = 6; p = 0.0004), and native gel/AFM assays supported a net inhibitory effect on amyloid formation.
- Bri2-23 was detected by HPLC/MS in conditioned media from BRI2-transfected cells and in human CSF from all samples tested, including three normal subjects shown.
Methods
- rAAV1 constructs expressing BRI2, BRI2-Aβ1-40, BRI2del244-266, eGFP, or nonspecific scFv were injected intracerebroventricularly into postnatal day 0 TgCRND8 or Tg2576 APP mice; controls totaled n = 20 (noninjection n = 4, PBS n = 4, eGFP n = 5, nonspecific scFv n = 7), and experimental groups were BRI2-Aβ1-40 (n = 11), BRI2 (n = 8), and BRI2del244-266 (n = 13).
- Aβ deposition was assessed by anti-total Aβ immunostaining, cortical plaque burden, Thio S-positive plaque counts, and Aβ end-specific ELISAs of SDS-soluble and formic acid-insoluble brain extracts; plasma Aβ and anti-Aβ IgG were also measured.
- In vitro aggregation was analyzed by native gel electrophoresis, thioflavin T fluorescence, and atomic force microscopy; Bri2-23 was detected by HPLC/mass spectrometry in cell media and human CSF.
Limitations
- The paper states it cannot completely rule out subtle effects on Aβ generation that could influence deposition, and that further study of BRI2/Bri2-23 and related peptides is required to fully understand their anti-amyloidogenic action and other functions.
- Evident from the text: in vivo evidence comes from APP transgenic mouse models with viral overexpression, not from endogenous BRI2 manipulation or human disease cohorts; human CSF evidence is limited to detection of Bri2-23 in normal CSF samples shown, and no cognitive or neurodegeneration outcomes are reported.
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Claims the paper makes
34 Own result · 17 Own interpretation · 7 No full text of the sources · 6 Partly supported · 4 Supported · 4 Sources not found · 4 Own method · 2 Not checked yet · 1 Supported so far · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Notably, synthetic ABri and ADan undergo rapid aggregation and fibrillization into amyloid, and they are neurotoxic (Gibson et al., 2005;Ghiso et al., 2006).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Introduction
What the sources say
- Not checked — no full text of the sourcecites Gibson et al., 2005 source
- Partly supportedcites Ghiso et al., 2006 sourceExperimental — accuracy not yet measured
The Abstract (page not provided) identifies ABri and ADan as amyloid peptides and reports that both form ion-channel-like structures in reconstituted membranes. The References name a study of ADan neurotoxicity, but the passages do not establish that synthetic ABri and ADan are both neurotoxic. (LLM, conf=0.68)
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“By crossing BRI2-A1-40 or BRI-A1-42 transgenic mice with Tg2576 mice, we previously demonstrated that A1-40 and A42 have opposing effects on amyloid deposition (McGowan et al., 2005;Kim et al., 2007).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Introduction
What the sources say
- Partly supportedcites McGowan et al., 2005 sourceExperimental — accuracy not yet measured
The Results report that crossing BRI-Aβ42 mice with Tg2576 mice markedly increased amyloid deposition. The Discussion reports that BRI-Aβ40 mice did not develop deposits on their own, but our copy does not report a BRI-Aβ40/Tg2576 cross or show that Aβ40 had an opposing effect on deposition in crossed mice. (LLM, conf=0.88)
- Partly supportedcites Kim et al., 2007 sourceExperimental — accuracy not yet measured
The Results section reports 60–90% less amyloid deposition in BRI-Aβ40/Tg2576 mice than in Tg2576 littermates. The Abstract states that Aβ42 promotes deposition while Aβ40 inhibits it, and the Generation of mice section says both BRI lines were crossed with Tg2576. But the passages do not establish the opposing effects on deposition by comparing both types of Tg2576 cross; the Aβ42 deposition evidence described in the Introduction concerns BRI-Aβ42 mice. (LLM, conf=0.84)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Notably, synthetic ABri and ADan undergo rapid aggregation and fibrillization into amyloid, and they are neurotoxic (Gibson et al., 2005;Ghiso et al., 2006).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Introduction
What the sources say
- Not checked — no full text of the sourcecites Gibson et al., 2005 source
- Partly supportedcites Ghiso et al., 2006 sourceExperimental — accuracy not yet measured
The Abstract identifies ABri and ADan as the main components of amyloid fibrils in familial British and Danish dementias. It does not establish that synthetic versions of both peptides aggregate or fibrillize rapidly; searches for “synthetic,” “aggregation,” and “fibrillization” found no passage reporting that behavior. (LLM, conf=0.82)
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.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Analyses of the biologic effects of mutations in the BRI2 (ITM2b) and the amyloid  precursor protein (APP) genes support the hypothesis that cerebral accumulation of amyloidogenic peptides in familial British and familial Danish dementias and Alzheimer's disease (AD) is associated with neurodegeneration.”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Abstract
What the sources say
- Supportedcites Golde, 2003 source
In “Toward a complete understanding of AD pathogenesis,” the paper describes British familial dementia and familial Danish dementia as disorders with amyloidogenic peptide accumulation, tangles, and neuronal loss, and links that accumulation to dementia. The same section describes APP mutations that increase or alter Aβ and evidence connecting Aβ to neurotoxicity in Alzheimer’s disease. (LLM, conf=0.91)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The reduction in A deposition observed in the mice expressing the rAAV1 BRI2-A1-40 transgene was consistent with our previous transgenic mice studies (Kim et al., 2007), whereas the reduction of A deposition observed in the mice expressing BRI2 was unexpected.”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > BRI2 and BRI2-A1-40 suppress amyloid deposition in APP transgenic mice
What the sources say
- Supportedcites Kim et al., 2007 source
The section on bitransgenic BRI-Aβ40/Tg2576 mice reports substantially reduced Aβ deposition compared with Tg2576 littermates. That transgenic finding supports the citing sentence’s claim that the later rAAV1 BRI2-Aβ1-40 result was consistent with the previous mouse studies; the cited paper need not have studied the rAAV1 mice themselves. (LLM, conf=0.92)
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.
- 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
“The studies with BRI2-A1-40 confirmed previous studies obtained using conventional transgenic mice expressing BRI2-A1-40 (McGowan et al., 2005;Kim et al., 2007).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Discussion
What the sources say
- Not checked yetcites McGowan et al., 2005 source
Checked before — its earlier verdict is held back until a new check runs.
- Supportedcites Kim et al., 2007 source
The Generation of mice section describes conventional transgenic mice expressing BRI-Aβ40. The results section reports that crossing these mice with Tg2576 mice markedly reduced amyloid deposition, making this paper an example of the earlier conventional-transgenic work identified by the citation. (LLM, conf=0.90)
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.
- Not checked yet
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
“BRI2-A1-40 expression slightly increased plasma A40 levels, attributable to brain to plasma efflux of A1-40; plasma A1-42 levels were not significantly changed by BRI2 expression (Fig. 2 D).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > BRI2 and BRI2-A1-40 suppress amyloid deposition in APP transgenic mice
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
“There was no evidence for an anti-A titer in any of the rAAV1injected mice (Fig. 2 F).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > BRI2 and BRI2-A1-40 suppress amyloid deposition in APP transgenic mice
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
“Additional data indicate that the 23 aa peptide, Bri23, released from BRI2 by normal processing, is present in human CSF, inhibits A aggregation in vitro and mediates its anti-amyloidogenic effect in vivo.”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Abstract
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.
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
“Expression of BRI2-A1-40 mimics the suppressive effect previously observed using conventional transgenic methods, further validating the somatic brain transgenic methodology.”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Abstract
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. 9
- It may state two separate claims as one. 10
Every source the paper cites for this claim was checked and supports it.
In the paper
“Indeed, genetic analyses of FBD, FDD, and familial forms of AD support a unifying pathologic mechanism in which accumulation of amyloidogenic peptides triggers a complex pathological cascade leading to neurodegeneration (Golde, 2003).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Introduction
What the sources say
- Supportedcites Golde, 2003 source
In “Toward a complete understanding of AD pathogenesis,” the paper says evidence from familial British dementia (called BFD in the copy) and familial Danish dementia further supports the amyloid-accumulation hypothesis. The same section describes genetic evidence from familial AD and a modified amyloid cascade leading to neuronal death and dysfunction. No page numbers are provided in the supplied copy. (LLM, conf=0.90)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Familial British and Danish dementias (FBD and FDD, respectively) are neurodegenerative dementias pathologically characterized by parenchymal preamyloid and amyloid deposits, cerebral amyloid angiopathy (CAA), neuronal loss, and neurofibrillary tangles (Ghiso et al., 2006).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Introduction
What the sources say
- Partly supportedcites Ghiso et al., 2006 sourceExperimental — accuracy not yet measured
The Abstract describes familial British and Danish dementias as having parenchymal pre-amyloid and amyloid deposits, cerebral amyloid angiopathy, and neurofibrillary tangles. It mentions neuronal loss specifically in relation to Alzheimer disease, not as an established pathological feature of both familial dementias, so that part of the citing sentence is not supported by our copy. (LLM, conf=0.84)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Disease-causing mutations result in the production of C-terminally extended 277 aa mutant BRI2 proteins, which are cleaved at the normal furin processing site to generate distinct 34 aa peptides (ABri in FBD and ADan in FDD) that accumulate in the brains of affected patients (Vidal et al., 1999(Vidal et al., , 2000)).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Introduction
What the sources say
- Not checked — no full text of the sourcecites Vidal et al., 1999 source
- Partly supportedcites Vidal et al., 2000 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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.
- Rests on an assumption: Two mutations in the ITM2b gene encoding the BRI2 protein cause familial British and familial Danish dementias.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Several methods were used, including a native gel assay previously used to demonstrate that A1-40 inhibits A1-42 aggregation (Kim et al., 2007).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Bri2-23 inhibits A1-42 aggregation in vitro
What the sources say
- Supportedcites Kim et al., 2007 source
The ‘Aβ40 inhibits Aβ42 aggregation in vitro’ section reports that adding Aβ40 reduced Aβ42 high-molecular-weight complex formation. Figure 8 describes the nondenaturing gel assay used to demonstrate this effect. (LLM, conf=0.95)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Beyond the genetic link to FDD and FBD, little is known about the function of BRI2 and its homologues.”
- Also stated in: § Discussion · plain
“Nevertheless, other than the genetic link between BRI2 and FBD and FDD, almost nothing is known about the function of the BRI proteins (Ghiso et al., 2006).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Discussion
What the sources say
- Partly supportedcites Ghiso et al., 2006 sourceExperimental — accuracy not yet measured
The Abstract states that FBD and FDD are linked to mutations in BRI2. Neither the Abstract nor the retrieved passages on BRI2 and its homologues state that little is known about the proteins’ functions, so that central part of the claim is not supported by our copy. (LLM, conf=0.76)
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.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When A1-42 aggregation was assessed using the native gel assay, we observed loss of the monomeric A1-42 signal and the appearance of high-molecular weight (HMW) aggregates (Fig. 3A, lane 10).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Bri2-23 inhibits A1-42 aggregation in vitro
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
“Coaggregation of A42 and Bri2-23 demonstrates that Bri2-23 appears to initially increase the rate of aggregate formation during the first 12 h of incubation, but inhibits fibril formation at later time points (Fig. 3C).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Bri2-23 inhibits A1-42 aggregation in vitro
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.
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
“Western blot analyses of brain lysates demonstrated that the somatic brain transgenic methodology produced approximately equivalent expression levels from the BRI2 and BRI2del244 -266 constructs and somewhat higher levels from BRI2-A1-40 (Fig. 4 E).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > The Bri2-23 sequence is required to suppress A deposition in vivo
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.
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
“CAA was not increased by the BRI transgenes and was almost completely absent in the TgCRND8 mice at 3 months of age.”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Discussion
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 claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Previous studies had demonstrated a potential interaction between BRI2 and APP and noted that BRI2 overexpression increased APP C-terminal fragment  (CTF) and reduced A secretion in cultured cells (Fotinopoulou et al., 2005;Matsuda et al., 2005).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > BRI2 and BRI2-A1-40 suppress amyloid deposition in APP transgenic mice
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. It may state two separate claims as one.
In the paper
“Endogenous mouse A levels were measured using the previously validated rodent-specific A ELISA system as previously reported (Eckman et al., 2006).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > A sandwich ELISA.
What the sources say
- Not checked — no full text of the sourcecites Eckman et al., 2006 source
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
“Expression of BRI2 was intended to serve as a second control, because we had established that rAAV1-hGFP delivery and mock virus delivery did not alter A deposition in the CRND8 APP mouse model (Levites et al., 2006b).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > BRI2 and BRI2-A1-40 suppress amyloid deposition in APP transgenic mice
What the sources say
- Not matchedcites Levites et al., 2006b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
It may state two separate claims as one.
- Not matched
None of the sources cited for this claim have been checked yet.
In the paper
“It is expressed at high levels in the brain and cleaved by furin or furin-like proteases at its C terminus to produce a 23 aa peptide (Bri2-23) (Kim et al., 1999;Choi et al., 2004) (Fig. 1 B).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Introduction
What the sources say
- Not checked — no full text of the sourcecites Kim et al., 1999 source
- Not matchedcites Choi et al., 2004
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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
“Previous studies had demonstrated a potential interaction between BRI2 and APP and noted that BRI2 overexpression increased APP C-terminal fragment  (CTF) and reduced A secretion in cultured cells (Fotinopoulou et al., 2005;Matsuda et al., 2005).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > BRI2 and BRI2-A1-40 suppress amyloid deposition in APP transgenic mice
What the sources say
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data show that Bri2-23 has a complex effect on aggregation of monomeric A1-42; however, both assays are consistent with a net inhibitory effect of Bri2-23 peptide on amyloid formation, presumably through inhibition of a later stage in fibril assembly.”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Bri2-23 inhibits A1-42 aggregation in vitro
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.
It may state two separate claims as one.
In the paper
“Notably, in FDD brains, A and the ADan peptide are codeposited and bind to each other in vitro (Tomidokoro et al., 2005).”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Discussion
What the sources say
- Not checked — no full text of the sourcecites Tomidokoro et al., 2005 source
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.
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
“Note that the forebrain and hippocampus are routinely transduced, whereas hindbrain structures (e.g., cerebellum) are more variably transduced.”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Discussion
plaincorrelationaln = 3- 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.
The paper relies on this without support.
Two mutations in the ITM2b gene encoding the BRI2 protein cause familial British and familial Danish dementias.
“Two mutations in the ITM2b gene encoding the BRI2 protein have been identified as the cause of FBD and FDD.”
The paper relies on this without support.
Anti-Aβ antibodies reduce Aβ deposition in mice.
“Because anti-A antibodies reduce A deposition in mice and expression of virally encoded A peptides in the periphery has been shown to generate an anti-A response, we examined whether CNS delivery of the transgene induced a humoral immune response to A.”
The paper relies on this without support.
Expression of virally encoded Aβ peptides in the periphery generates an anti-Aβ response.
“Because anti-A antibodies reduce A deposition in mice and expression of virally encoded A peptides in the periphery has been shown to generate an anti-A response, we examined whether CNS delivery of the transgene induced a humoral immune response to A.”
The paper relies on this without support.
Because of the rapid onset of Aβ deposition in TgCRND8 mice, it is not possible to measure steady-state Aβ levels.
“Because of the rapid onset of A deposition in TgCRND8 mice, it is not possible to measure steady-state A levels; therefore, we conducted additional experiments in Tg2576 mice to determine whether BRI2 altered steady-state A before plaque deposition.”
The paper relies on this without support.
First-generation antibodies were not sensitive enough to detect the Bri2-23 peptide in biological samples.
“First-generation antibodies were not sensitive enough to detect the Bri2-23 peptide in biological samples.”
The paper relies on this without support.
BRI2del244-266 encodes a protein containing the region of BRI2 previously shown to interact with APP and interfere with APP processing in cell culture.
“BRI2del244 -266 encodes a protein containing the region of BRI2 previously shown to interact with APP and interfere with APP processing in cell culture.”
The paper relies on this without support.
BRI2 and BRI2-A1-40 are cleaved by furin and other kex2 proteases to release Bri2-23 and A1-40, respectively.
“BRI2 and BRI2-A1-40 are cleaved by furin and other kex2 proteases to release Bri2-23 and A1-40, respectively.”
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
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Mouse anti-A IgG ELISA.
“Images are shown in amplitude mode, where increasing brightness indicates greater damping of cantilever oscillation.”
§ Neurobiology of Disease BRI2 (ITM2b) Inhibits A Deposition In Vivo > Discussion
“D, AFM analysis of aggregates at 72 h of incubation.Representative images, shown in height mode, are 10 ϫ 10 m.”
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“The AAV1 was prepared as described in Kim et al. (2008).”
MethodSelf-citationBRICHOS Domains Efficiently Delay Fibrillation of Amyloid β-Peptide
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“Cortical tissues were lysed in 0.2% diethylamine/50 mM NaCl lysis buffer with EDTA-free protease inhibitor mixture (Roche) by sonication, as previously described (Kim et al., 2008).”
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“1 (1:1000; human Ab40 specific) [23].”
BackgroundMethodSelf-citationHippocampal expression of murine IL-4 results in exacerbation of amyloid deposition
Chakrabarty, P., Tianbai, L., Herring, A., Ceballos-Diaz, C., Das, P., & Golde, T. E. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-36 · Cited by 116
“AAV1 viruses expressing mIL-4 or EGFP, under the control of the cytomegalovirus enhancer/chicken β actin promoter were generated as described previously [19].”
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Disease Biomarkers in Multiple Sclerosis
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“which mutations produce CNS amyloid deposition in humans, also inhibit Ab fibril formation [213-216] (Table 1).”
BackgroundMatsuda, S., Giliberto, L., Matsuda, Y., McGowan, E. M., & D'adamio, L. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2094-08.2008 · Cited by 96
“A study published while we were revising our manuscript indicates that the Bri2-23 peptide released from the BRI2 protein by furin/furin-like protease cleavage can inhibit A aggregation in vitro and that overexpression of BRI2 reduced A deposition in APP CRND8 mice (Kim et al., 2008).”
BackgroundShort Aβ peptides attenuate Aβ42 toxicity in vivo
Moore, B. D., Martin, J., de Mena, L., Sánchez, J., Cruz, P. E., Ceballos‐Diaz, C., Ladd, T. B., Ran, Y., Levites, Y., Kukar, T. L., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170600 · Cited by 89
“To examine whether Aβ38 expressed from rAAV vectors encoding BRI2-Aβ38 altered phenotypes in TgCRND8 mice, we expressed rAAV-BRI2-Aβ38, rAAV-BRI2-Aβ40, rAAV-BRI2-Stop, and rAAV-EGFP vectors from P0 to 9 mo in TgCRND8 mice and non-Tg (NTg) littermates.”
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Self-citationRetractedThe BRICHOS Domain, Amyloid Fibril Formation, and Their Relationship
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“As a consequence, BRI2 modulates APP processing inhibiting Aβ formation and deposition properties, a feature observed in both cell culture and mouse models of AD [125–128].”
BackgroundMatsuda, S., Matsuda, Y., Snapp, E. L., & D'adamio, L. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.08.005 · Cited by 70
“The findings that BRI2ΔC23 is retained in the ER and does not inhibit APP processing help explain why BRI2ΔC23 fails to reduce formation of pathogenic amyloid plaques in the brain of the AD mouse model (Kim et al., 2008).”
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Self-citationAmyloid precursor protein-induced axonopathies are independent of amyloid-β peptides
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“rAAV serotype 2/1 expressing human wild-type, A53T or E46K αS under the control of the CMV early enhancer/chicken β actin (CAG) promoter, were generated as described previously [60].”
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Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits
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“The extraction and ELISA methods used have been described previously [25], with minor modification.”
MethodSelf-citationHoldase activity of secreted Hsp70 masks amyloid-β42 neurotoxicity in Drosophila
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“Although having more limited and variable expression compared to traditional transgenic models, SBT still allows for rapid, widespread expression and screening of genes of interest before expending the time and expense developing traditional transgenic models [12, 13].”
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BRI2-BRICHOS is increased in human amyloid plaques in early stages of Alzheimer's disease
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Depleting Trim28 in adult mice is well tolerated and reduces levels of α-synuclein and tau
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“The conditions are characterised by significant neuronal loss, a loss of cognitive and memory functions, disruptions to muscle movement and the induction of special rigidity [66,67].”
BackgroundModeling familial British and Danish dementia
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“V717F AbPP mice (Kim et al. 2008).”
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CEREBRAL AMYLOID ANGIOPATHY AND ALZHEIMER'S DISEASE.
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“Moreover, Bri2 suppresses A deposition, suggesting that the levels and/or activity of Bri2 can play a role in Alzheimer disease (41).”
BackgroundAudo, I. S., Bujakowska, K. M., Orhan, E., Shamieh, S. E., Sennlaub, F., Guillonneau, X., Antonio, A., Michiels, C., Lancelot, M., Letexier, M., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt439 · Cited by 35
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“Others have argued that the BRI2-23 wild type C-terminal peptide, released from BRI2 by furin/furin-like cleavage, can inhibit Ab aggregation in vitro [18].”
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“0011), regulates the processing of amyloidbeta and inhibits amyloid aggregation (53).”
BackgroundCerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis
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“Additionally, two molecules, Bri2 and Bri2-23 have been shown to interact with APP and regulate Aβ42 cleavage and aggregation in vivo [124, 125].”
BackgroundBri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis
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“, Cortica Neuroscience; A production-inhibiting BRI2-derived peptides for the intranasal administration to AD patients [926–933])”
BackgroundThe role of the integral type II transmembrane protein BRI2 in health and disease
Martins, F., Santos, I., Silva, O. A. B. D. C. E., Tambaro, S., & Rebelo, S. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03932-5 · Cited by 28
BRI2 as a central protein involved in neurodegeneration
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“Interestingly, virally delivered BRI2 in APP transgenic mice also reduced Aβ deposition [36].”
BackgroundTDPAC and β -NMR applications in chemistry and biochemistry
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Neuro-Immuno-Gene- and Genome-Editing-Therapy for Alzheimer’s Disease: Are We There Yet?
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“BRI2-23 peptide have revealed that BRI2-23 sequence is required to suppress A deposition in vivo [69].”
BackgroundChu, J., Li, J.-G., Ceballos‐Diaz, C., Golde, T. E., & Praticò, D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.012 · Cited by 28
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“Inaddition,bothviraldelivery of wtBRI2 and crossing an AD mouse model with wtBRI2 mice reduced AD pathology [8, 38, 103].”
InfluentialTamayev, R., & D'adamio, L. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5193-11.2012 · Cited by 23
“BRI2 is a physiological interactor of APP and regulates APP metabolism (Fotinopoulou et al., 2005; Matsuda et al., 2005, 2008, 2011b; Kim et al., 2008; Kilger et al., 2011).”
BackgroundTodd, K. L., Ghiso, J. A., & Rostagno, A. A. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.10.003 · Cited by 22
“In contrast, and in accordance with its presence in CSF in normal individuals (Zougman et al., 2008; Kim et al., 2008) and its lack of aggregability, Bri1-23 did not provoke a similar neurotoxic response even when bearing N-terminal pE.”
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Amelogenins: Multi-Functional Enamel Matrix Proteins and Their Binding Partners
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The inhibitory action of the chaperone BRICHOS against the α-Synuclein secondary nucleation pathway
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Fernández-Fúnez, P., Zhang, Y., Sanchez-Garcia, J., de Mena, L., Khare, S., Golde, T. E., Levites, Y., & Rincón-Limas, D. E. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv321 · Cited by 19
“Aß42 was captured with mAb 213 (human Aß35-42 specific) and detected by HRP-conjugated mAb Ab9 (40).”
MethodSelf-citationMarcora, M. S., Fernández-Gamba, A. C., Avendaño, L. A., Rotondaro, C., Podhajcer, O. L., Vidal, R., Morelli, L., Ceriani, M. F., & Castaño, E. M. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-5 · Cited by 19
“Other studies have reported that BRI2 may modulate amyloid β precursor protein (AβPP) processing in transfected cells and in transgenic mice leading to a reduced Aβ production and aggregation [20,21].”
Tambini, M. D., & D'adamio, L. (2020) · Scientific Reports · doi:10.1038/s41598-020-60800-1 · Cited by 16
Endogenous Human Proteins Interfering with Amyloid Formation
Gharibyan, A. L., Jayaweera, S. W., Lehmann, M., Anan, I., & Olofsson, A. (2022) · Biomolecules · doi:10.3390/biom12030446 · Cited by 17
Campo, M. D., Stargardt, A., Veerhuis, R., Reits, E. A., & Teunissen, C. E. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.01.036 · Cited by 16
Janus, C., & Golde, T. E. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.11.010 · Cited by 16
Self-citationWidespread Neuronal Transduction of the Rodent CNS via Neonatal Viral Injection
Kim, J., Grunke, S. D., & Jankowsky, J. L. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-3271-9_17 · Cited by 15
Self-citationBRI2 as an anti-Alzheimer gene
Matsuda, S., & Senda, T. (2018) · Medical Molecular Morphology · doi:10.1007/s00795-018-0191-1 · Cited by 13
First identification of ITM2B interactome in the human retina
Wohlschlegel, J., Argentini, M., Michiels, C., Letellier, C., Forster, V., Condroyer, C., He, Z., Thuret, G., Zeitz, C., Léger, T., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-96571-6 · Cited by 13
Peptidomic Approaches and Observations in Neurodegenerative Diseases
Muqaku, B., & Oeckl, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137332 · Cited by 12
BRI2 ectodomain affects Aβ42 fibrillation and tau truncation in human neuroblastoma cells
Campo, M. D., Oliveira, C. R., Scheper, W., Zwart, R., Korth, C., Müller‐Schiffmann, A., Kostallas, G., Biverstål, H., Presto, J., Johansson, J., et al. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1769-y · Cited by 12
Maccioni, R., Travisan, C., Badman, J., Zerial, S., Wagener, A., Andrade‐Talavera, Y., Picciau, F., Grassi, C., Chen, G., Lemoine, L., et al. (2024) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2024.102585 · Cited by 11
“In addition, several pieces of evidence connected BRI2, an SPPL2b substrate, to AD (Kim et al., 2008; Martins et al., 2021).”
Nagler, J. J., Cavileer, T., Hunter, S., et al. (2011) · Molecular Reproduction and Development · doi:10.1002/mrd.21277 · Cited by 10
“Human integral membrane protein 2B inhibits beta-amyloid deposition in nervous tissue associated with dementia-type neurogenerative diseases (Kim et al., 2008).”
BackgroundMechanisms of increased Alzheimer’s disease pathology with R47H and R62H TREM2 variants
Fancy, N. N., Willumsen, N., Chau, V. M. N., Boulger, S. L., Whitwell, H. J., Wang, W., Avot, B., Thomas, M., Talbot-Martin, J., Tsartsalis, S., et al. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03036-z · Cited by 8
“The R62H heterozygote samples showed increased expression of HLA-A and SRGAP3 transcripts involved in ‘phagocytotic vesicle’, and APOE and PICALM involved in extracellular ‘β-amyloid binding’ [30, 41].”
March, A., Borchelt, D., Golde, T. E., & Janus, C. (2014) · PubMed Central · Cited by 9
Self-citationAhmed, R., & Melacini, G. (2020) · Biophysical Chemistry · doi:10.1016/j.bpc.2020.106508 · Cited by 8
Arber, C., Casey, J. M., Crawford, S., Rambarack, N., Yaman, Ü., Wiethoff, S., Augustin, E., Piers, T. M., Price, M., Rostagno, A. A., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02820-z · Cited by 8
A Novel c.800G>C Variant of the ITM2B Gene in Familial Korean Dementia
Rhyu, J.-M., Park, J., Shin, B., Kim, Y.-E., Kim, E., Kim, K. W., & Cho, Y. G. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230051 · Cited by 7
“Second, BRI2 lost its original function of suppression of A (cid:2) formation and deposition [3, 15].”
Łuczkowski, M., Ricco, R. D., Stachura, M., Potocki, S., Hemmingsen, L., & Valensin, D. (2015) · Metallomics · doi:10.1039/c4mt00274a · Cited by 7
Kumar, G., Sarker, S., Menanteau‐Ledouble, S., et al. (2015) · Parasitology Research · doi:10.1007/s00436-015-4425-z · Cited by 7
“A hallmark of several metabolic diseases is protein misfolding (Kim et al. 2008).”
InfluentialAmyloids as Sensors and Protectors (ASAP) Hypothesis
Chapa, R. P., Emery, M. A., Fawver, J. N., & Murray, I. V. J. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-112015 · Cited by 7
Smirnova, E. V., Rakitina, T. V., Saratov, G. A., Kudriaeva, A. A., & Belogurov, A. A. (2022) · Crystals · doi:10.3390/cryst12020197 · Cited by 6
“This function as a modulator of APP processing is associated with Bri2 maturation, which started with furin-dependent cleavage of the C-terminal 23 amino acid long Bri23 peptide from immature Bri2 during its transport in the Golgi [34].”
BackgroundInfluentialCaramello, A., Fancy, N. N., Tournerie, C., Eklund, M., Chau, V. M. N., Adair, E., Papageorgopoulou, M., Jackson, J., Hardy, J., & Matthews, P. M. (2023) · medRxiv · doi:10.1101/2023.11.23.23298911 · Cited by 6
DEEP PHENOTYPING AND FURTHER INSIGHTS INTO ITM2B-RELATED RETINAL DYSTROPHY
Nassisi, M., Wohlschlegel, J., Liu, B., Letellier, C., Michiels, C., Aubois, A., Mohand‐Saïd, S., Habas, C., Sahel, J., Zeitz, C., et al. (2020) · Retina · doi:10.1097/iae.0000000000002953 · Cited by 5
Daude, N., Lee, I., Kim, T., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149410 · Cited by 5
Song, M., Song, K., Kim, S., Lee, J.-Y., Hwang, S., & Han, C. (2018) · Genes · doi:10.3390/genes9030160 · Cited by 4
“The BRICHOS domain of BRI2 also efficiently prevents fibrillation of amyloid β-peptide in vivo [30].”
The roles of GxxxG motif and gamma-secretase components in APP processing
Kim, J. (2009) · Interdisciplinary Bio Central · doi:10.4051/ibc.2009.4.0015 · Cited by 3
Self-citationDeterminants for Substoichiometric Inhibition of IAPP and Aβ Amyloid Aggregations by Bri2 BRICHOS
Zhang, Z., Huang, G., Gupta, S., Sargent, E., Tang, H., & Ding, F. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00839 · Cited by 3
Network analysis identifies strain-dependent response to tau and tau seeding-associated genes
Acri, D. J., You, Y., Tate, M. D., Karahan, H., Martinez, P., McCord, B., Sharify, A. D., John, S., Kim, B., Dabin, L. C., et al. (2023) · Journal of Experimental Medicine · doi:10.1084/jem.20230180 · Cited by 3
“We used an AAV-mediated gene expression model, as described before (Carlomagno et al., 2019; Cook et al., 2015; Kim et al., 2008).”
Self-citationPresto, J., & Johansson, J. (2015) · Springer briefs in molecular science · doi:10.1007/978-3-319-16564-6_1 · Cited by 3
Badman, J., Parracino, A., Kumar, R., & Tambaro, S. (2025) · Science Signaling · doi:10.1126/scisignal.adt2272 · Cited by 3
Shahidehpour, R. K., Nelson, P. T., Srinivasan, S., Zhong, Y., & Bachstetter, A. D. (2025) · Neuropathology · doi:10.1111/neup.70003 · Cited by 2
Metadata
- Authors
- Kim, J., Miller, V. M., Levites, Y., West, K. J., Zwizinski, C. W., Moore, B. D., Troendle, F. J., Bann, M., Verbeeck, C., Price, R. W., Smithson, L., Sonoda, L., Wagg, K., Rangachari, V., Zou, F., Younkin, S. G., Graff-Radford, N., Dickson, D., Rosenberry, T., & Golde, T. E.
- Affiliations
- Mayo Clinic (US)
- Mayo Clinic in Florida (US)
- ORCID
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-06-04
- Volume
- 28
- Issue
- 23
- Pages
- 6030-6036
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2586000
- OpenAlex
- W1992813803
- Semantic Scholar
- 6a6f30c6cabc6ff3434b78e2b58819c3fa74166a
- Cited by
- 113
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 1 · 2018: 6 · 2017: 2 · 2016: 4 · 2015: 16 · 2014: 7 · 2013: 8 · 2012: 10
- FWCI
- 5.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- American Heart Association
- Mayo Foundation for Medical Education and Research (AG17216, AG03949)
- National Institutes of Health (5p01ag003949-40, AG03949, AG17216)
- National Institute on Aging (P01-AG003949, AG03949, P50AG025711, R01 AG18454, P01AG025531, R01AG018454, P01 AG 017216)
- 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
- BRI2, ITM2B, amyloid-beta deposition, Aβ40, Alzheimer's disease, familial British dementia, familial Danish dementia, cerebrospinal fluid, amyloid aggregation inhibition
- MeSH terms
- Dependovirus, Amyloid, Animals, Brain, Chickens, Female, Cricetinae, Humans, Male, Membrane Glycoproteins, Membrane Proteins, Mice, Transgenic, Peptide Fragments, Phenotype, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Gene Transfer Techniques, Adaptor Proteins, Signal Transducing, Mice
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 2026-10-17, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-17 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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Statistics and arithmetic are recomputed, not judged.
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