The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index; none of the 32 sources its claims cite is checked for support yet.
Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Open accessAbstract
Biochemical and immunocytochemical analyses were performed to evaluate the composition of the amyloid beta protein (A beta) deposited in the brains of patients with Alzheimer's disease (AD). To quantitate all A beta s present, cerebral cortex was homogenized in 70% formic acid, and the supernatant was analyzed by sandwich enzyme-linked immunoabsorbent assays specific for various forms of A beta. In 9 of 27 AD brains examined, there was minimal congophilic angiopathy and virtually all A beta (96%) ended at A beta 42(43). The other 18 AD brains contained increasing amounts of A beta ending at A beta 40. From this set, 6 brains with substantial congophilic angiopathy were separately analyzed. In these brains, the amount of A beta ending at A beta 42(43) was much the same as in brains with minimal congophilic angiopathy, but a large amount of A beta ending at A beta 40 (76% of total A beta) was also present. Immunocytochemical analysis with monoclonal antibodies selective for A beta s ending at A beta 42(43) or A beta 40 confirmed that, in brains with minimal congophilic angiopathy, virtually all A beta is A beta ending at A beta 42(43) and showed that this A beta is deposited in senile plaques of all types. In the remaining AD brains, A beta 42(43) was deposited in a similar fashion in plaques, but, in addition, widely varying amounts of A beta ending at A beta 40 were deposited, primarily in blood vessel walls, where some A beta ending at A beta 42(43) was also present. These observations indicate that A beta s ending at A beta 42(43), which are a minor component of the A beta in human cerebrospinal fluid and plasma, are critically important in AD where they deposit selectively in plaques of all kinds.
Overview
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Written from the paper’s full text.
TL;DR
In Alzheimer’s disease (AD) brain, Aβ ending at Aβ42(43) is the predominant deposited species in cases with minimal congophilic angiopathy, while Aβ40 becomes prominent mainly in brains with substantial vascular amyloid. The authors conclude that Aβ42(43), though a minor secreted species, is critically important in AD because it deposits selectively in senile plaques of all types.
Key findings
- In 9 of 27 AD brains with minimal congophilic angiopathy, virtually all Aβ (96%) ended at Aβ42(43); BC-05/4G8 detected 4663 ± 421 pmol/g versus BAN-50/BC-05 at 714 ± 68 pmol/g, while BA-27/4G8 detected only 216 ± 38 pmol/g.
- In 6 AD brains with substantial congophilic angiopathy, Aβ42(43) amounts were similar to minimal-angiopathy brains (BC-05/4G8: 5089 ± 409 pmol/g; BAN-50/BC-05: 826 ± 119 pmol/g), but Aβ40 was dramatically increased (BA-27/4G8: 13,607 ± 3397 pmol/g; BAN-50/BA-27: 5001 ± 2164 pmol/g). The abstract reports 76% of total Aβ ended at Aβ40 in these brains; the Results state an average of 67%.
- Total Aβ in 27 AD brains ranged from at least 500 to 4400 times that in plaque-free control brain; 98.5% of total Aβ required formic acid for solubilization and only 1.5% was extracted into Tris-saline.
- Immunocytochemistry showed BC-05 and 4G8 intensely labeled all plaque types and vascular amyloid, whereas BA-27 stained vascular amyloid well but stained plaque cores less intensely and almost failed to stain uncored plaques.
Methods
- AD and plaque-free control cerebral cortex was homogenized directly in 70% formic acid or sequentially extracted first into Tris-saline buffer with protease inhibitors and then into 70% formic acid.
- Aβ was quantitated by sandwich ELISAs specific for forms ending at Aβ40 (BA-27/4G8 or BAN-50/BA-27) or Aβ42(43) (BC-05/4G8 or BAN-50/BC-05), with some samples fractionated by Superose 12 size exclusion chromatography.
- Samples included an initial 3 AD and 3 control brains, then 27 AD and 6 plaque-free control brains; immunocytochemistry used formalin- or methacarn-fixed inferior temporal cortex with BA-27, BC-05, and 4G8 antibodies.
Limitations
- The paper does not state a formal limitations section. The authors note that BAN-50 cannot capture Aβs beginning at or beyond Aβ17, so the increased Aβ detected with 4G8 may indicate considerable amino-terminally truncated Aβ, but they caution this interpretation because other factors such as isoaspartates at Aβ1 and Aβ37 may diminish BAN-50 capture.
- The authors address the concern that BA-27 epitope destruction during fixation could distort immunocytochemistry, arguing against it because brains with minimal vascular amyloid had virtually all Aβ ending at Aβ42(43).
- Evident from the text: subgroup analyses rely on small numbers (e.g., 9 minimal and 6 substantial congophilic angiopathy cases), and no formal statistical comparisons are reported.
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25 Own result · 10 No full text of the sources · 6 Own method · 4 Not checked yet · 4 Own interpretation · 2 Sources not found · 1 No basis given
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In the paper
“and large amounts of A{3C40 were deposited in some brains (Fig. 2).”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
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In the paper
“the remaining brains had increasing amounts of A{3C40'”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
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In the paper
“Based on this upper limit, the total A{3 in the 27 AD brains ranged from at least SOO to 4400 times that in plaque-free control brain.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The recovery of synthetic Aβ added to control brain applies to endogenous Aβ in AD brain.
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 brains, A{3C40' measured with BA-27/4G8 (13607 :+: 3397 pmol/g) and BAN-SOIBA-27 (SOOI :+: 2164 pmol/g) ELISAs, was dramatically increased.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In many AD brains, virtually all A{3 was A{3C42(4:Jl'”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
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In the paper
“and showed that this Ap is deposited in senile plaques of all types.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
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In the paper
“In the remaining AD brains, Ap42(43) was deposited in a similar fashion in plaques”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
plainn = 18- Asserted: passes — The authors put it forward as true.
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In the paper
“but, in addition, widely varying amounts of Ap ending at Ap40 were deposited, primarily in blood vessel walls”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
plainn = 18- Asserted: passes — The authors put it forward as true.
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In the paper
“but a large amount of Ap ending at Ap40 (76% of total Am was also present.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
plaincorrelationaln = 6- Asserted: passes — The authors put it forward as true.
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In the paper
“but the total A{3 present in control brain was invariably less than 7 pmol/g.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
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In the paper
“The BAN-50IBA-27 ELISA showed a total of 73 ± 28 pmol of A{3lg in AD brain, whereas the BAN-50/BC-05 ELISA detected 725 ± 347 pmol/g (Table I).”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > EXPERIMENTAL PROCEDURES
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In the paper
“In the AD brains, 98.S% of the total A{3 present required formic acid for solubilization and only l.S9t}was extracted into Tris-saline.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
plainn = 27- Asserted: passes — The authors put it forward as true.
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In the paper
“Both 4G8 and BC-OS intensely labeled the AD brain, whereas BA-27 showed very little labeling (Fig. 3).”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Sandwich ELISAs for A~Sandwich
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In the paper
“BA-27 stained vascular amyloid quite well but, in contrast to BC-OS and 4G8, stained the cores of classic neuritic plaques less intensely and almost completely failed to stain uncored (diffuse and uncored neuritic) plaques or the region surrounding plaque cores.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Sandwich ELISAs for A~Sandwich
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In the paper
“4G8 and BC-OS labeled uncored (diffuse and uncored neuritic) plaques, the cores of classic neuritic plaques, the region surrounding plaque cores, and vascular amyloid.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Sandwich ELISAs for A~Sandwich
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In the paper
“In 9 of 27 AD brains examined, there was minimal congophilic angiopathy and virtually all Ap (96%) ended at AP42(43).”
- Also stated in: § Analysis of A{3 in 27 AD and 6 · plain
“Virtually all A{3 in the formic acid extracts from these 9 brains (96%) ended at A{342(43)”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
plaincorrelationaln = 9- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Analysis of A{3 in 27 AD and 6 · plain
In the paper
“The immunocytochemical results shown here and in a recent report by Iwatsubo et al. (21) demonstrate that BC-05 intensely stains all types of senile plaques, that vessels are stained by both BC-OS and BA-27, and that BA-27 stains plaques poorly, in many cases only faintly staining occasional cored plaques (Fig. 3).”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Sandwich ELISAs for A~Sandwich
What the sources say
- Not checked — no full text of the sourcecites [21] Iwatsubo, 1994, Neuron source
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In the paper
“In the 3 AD brains, the BA-27/4GB ELISA showed a total of93 ± 45 pmol of A,B/g whereas the BC-05/4G8 ELISA showed 3200 ± 1350 pmol of A,BIg (Table I).”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > EXPERIMENTAL PROCEDURES
plainn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, it a ppears t hat deposition of A{3C42(43) in senile plaq ues is fundamental to AD path ogenesis with additi ona l deposition of A{3C40' prim aril y in blood vessel wa lls, occurring in some cases.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
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In the paper
“Th is finding is consistent with pr evious re ports (15,17,18) that most of the A{3 in AD brains is amino-ter mi na lly trunca te d or modifi ed.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > FIG.
What the sources say
plainn = 27- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“The monoclonal antibodies employed were BAN-50 (anti-A{31-16), 4G8 (anti-Af3l7-24) (19), BA-27, which is specific for A{3 ending at A{340, and BC-05, which is specific for A{3 ending at A{342(43).”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Sandwich ELISAs for A~Sandwich
What the sources say
- Not checked — no full text of the sourcecites [9] Suzuki, 1994, Science source
- Not checked yetcites [19] Kim, 1988, Neurosci. Res. Commun.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In the brains of patients with Alzheimer's disease (AD),!amyloid composed of 4-kDa amyloid {3 protein (A{3) is deposited in senile plaques and in blood vessel walls.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
What the sources say
- Not checked — no full text of the sourcecites [1] Yamaguchi, 1988, Acta Neuropathol. source
- Not matchedcites [2] Masliah, 1990, Am. J. Pathol.
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.
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In the paper
“Recently, we and others have shown that normal processing of the large amyloid f3 protein precursor ({3-APP) secretes 4-kDa A(3 that is readily detected in human cerebrospinal fluid and in medium conditioned by cultured cells (3)(4)(5)(6).”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“As t his occurred, BC-05 in varia bly showed intense staini ng of all plaq ues as well as some staining of blood ves sel wa lls whereas BA-27 intensely staine d blood vess els a nd showed increa sing stai ning of A{3C40 in plaques, par ticul a rly ma t ure cored pla qu es, a lthough it never stained plaques to t he exte nt observed with BC-05.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
What the sources say
- Not matchedcites [22] Iwatsubo, 1995, Ann. Neurol.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Recent reports using this approach, particularly those of Roher and his colleagues, indicate that the SDS-insoluble amyloid in senile plaque cores is primarily A(31-42 (15,17)”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“In th ese br ai ns, A{3C42(43l staine d by BC-05 was deposited fir st in diffu se plaq ues , an d there was esse ntia lly no staining by BA-27.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
What the sources say
- Not matchedcites [22] Iwatsubo, 1995, Ann. Neurol.
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.
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The paper relies on this without support.
The recovery of synthetic Aβ added to control brain applies to endogenous Aβ in AD brain.
“To assess Af3 recovery, synthetic Af3 (500 pmol of A{31-4o plus 500 pmol of Af31-42, Bachem) was added to samples of cerebral cortex (-0.5 g) from control brains prior to homogenization.”
Claims other papers make about this one
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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
“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).”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Gravina et al., 1995
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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.”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Gravina et al., 1995
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the 30% in which A40 was the predominant species deposited, there was typically prominent congophilic angiopathy.”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Gravina et al., 1995
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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).”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Gravina et al., 1995
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“accumulates to a variable degree in the human AD brain”
From Aβ40 Inhibits Amyloid Deposition In Vivo (2007) · cites this paper as Gravina et al., 1995
The cited source says what the claim attributes to it.
In the citing 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.”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Gravina et al., 1995
The cited source says what the claim attributes to it.
In the citing 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).”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Gravina et al., 1995
In the citing paper
“In contrast, Aβ40, the major Aβ peptide secreted by cells, appears to be the predominant species deposited in the amyloid deposits in the cerebral vasculature (congophillic angiopathy, CAA) (Gravina et al., 1995; Iwatsubo et al., 1994).”
From Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice (2005) · cites this paper as Gravina et al., 1995
In the citing paper
“These data provide definitive in vivo confirmation of predictions inferred from (1) in vitro studies of Aβ aggregation, (2) effects of PS and certain APP mutations on Aβ production and deposition, and (3) analyses of Aβ peptides in the human AD brain (Gravina et al., 1995; Iwatsubo et al., 1994).”
From Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice (2005) · cites this paper as Gravina et al., 1995
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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 major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Abstract
“In these brains, the amount of Ap ending at AP42(43) was much the same as in brains with minimal congophilic angiopathy, but a large amount of Ap ending at Ap40 (76% of total Am was also present.”
§ Communication Amyloid 13 Protein (Af3) in Alzheimer's Disease Brain BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSIS WITH ANTIBODIES SPECIFIC FOR FORMS ENDING AT A1340 OR AI342(43)* ( > Analysis of A{3 in 27 AD and 6
“On average, 67% of the A{3 in brains with substantial congophilic angiopathy ended at A{340”
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“The direct toxicity of not only AA1Y40 and AA1Y42 but also their degradation products, therefore, likely depends on how they combine to form assemblies in vivo because conversion from oligomers to protofibrils to fibrils is associated with a reduction in directly mediated damage to synapses and neurons (77).”
BackgroundInfluentialDual-functional nanoparticles targeting amyloid plaques in the brains of Alzheimer's disease mice
Zhang, C., Xu, W., Zheng, X., Shao, X., Liu, Q., Zhang, Q., & Qian, Y. J. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.09.063 · Cited by 266
“Ab1-42 is the predominant species of Ab peptide (approximately 96% the total) [11] and its monomer is the most toxic isoform because it has a strong tendency toward aggregation [12], although its protofibrillar and fibrillar aggregates are also toxic [13,14].”
BackgroundMetformin attenuates Alzheimer’s disease-like neuropathology in obese, leptin-resistant mice
Li, J., Deng, J., Sheng, W., & Zuo, Z. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2012.03.002 · Cited by 260
“Aβ1-42 assay Aβ was extracted from brain tissues as described before (Gravina et al., 1995).”
MethodAge but Not Diagnosis Is the Main Predictor of Plasma Amyloid β-Protein Levels
Fukumoto, H., Tennis, M. K., Locascio, J. J., Hyman, B. T., Growdon, J. H., & Irizarry, M. C. (2003) · Archives of Neurology · doi:10.1001/archneur.60.7.958 · Cited by 258
On the Seeding and Oligomerization of pGlu-Amyloid Peptides (in vitro)
Schilling, S., Lauber, T., Schaupp, M., Manhart, S., Scheel, E., Böhm, G., & Demuth, H.-U. (2006) · Biochemistry · doi:10.1021/bi0612667 · Cited by 254
Kanai, M., Matsubara, E., Isoe, K., Urakami, K., Nakashima, K., Arai, H., Sasaki, H., Abe, K., Iwatsubo, T., Kosaka, T., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410440108 · Cited by 340
Hartz, A. M. S., Bauer, B., Soldner, E. L. B., Wolf, A., Boy, S., Backhaus, R., Mihaljevic, I., Bogdahn, U., Klünemann, H. H., Schuierer, G., et al. (2012) · Stroke · doi:10.1161/strokeaha.111.627562 · Cited by 248
Amyloid β-Protein Monomer Folding: Free-Energy Surfaces Reveal Alloform-Specific Differences
Yang, M., & Teplow, D. B. (2008) · Journal of Molecular Biology · doi:10.1016/j.jmb.2008.09.039 · Cited by 255
Association of Plasma β-Amyloid Level and Cognitive Reserve With Subsequent Cognitive Decline
Yaffe, K. S. (2011) · JAMA · doi:10.1001/jama.2010.1995 · Cited by 245
Sporadic cerebral amyloid angiopathy: pathology, clinical implications, and possible pathomechanisms
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“Ab fibrils that have been shown in vascular tunica media in close contact with smooth muscle cells were mainly composed of Ab40 [4, 28, 122, 146, 147, 149], while Ab42 was present in only some deposits in AD [4, 35] and in Down’s syndrome [68].”
BackgroundJankowsky, J. L., Slunt, H. H., Gonzales, V., Savonenko, A. V., Wen, J. C., Jenkins, N. A., Copeland, N. G., Younkin, L. H., Lester, H. A., Younkin, S. G., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020355 · Cited by 237
Self-citationIntrinsic disorder in proteins associated with neurodegenerative diseases
Vladimir, N. (2009) · Frontiers in bioscience · doi:10.2741/3594 · Cited by 241
“in patients afflicted with early onset AD [102, 103], and because of the greater in vitro tendency of the Aβ1–42 to aggregate and precipitate as amyloid [104, 105].”
BackgroundMehta, P. D., Pirttilä, T., Patrick, B. A., Barshatzky, M., & Mehta, S. P. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(01)01754-2 · Cited by 233
Kelleher, R. J., & Soiza, R. L. (2013) · Europe PMC (PubMed Central) · Cited by 232
Identification of early pericyte loss and vascular amyloidosis in Alzheimer’s disease retina
Shi, H., Koronyo, Y., Rentsendorj, A., Regis, G. C., Sheyn, J., Fuchs, D.-T., Kramerov, A. A., Ljubimov, A. V., Dumitrascu, O. M., Rodriguez, A. R., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02134-w · Cited by 230
Combination assay of CSF Tau, Aβ1-40 and Aβ1-42(43) as a biochemical marker of Alzheimer's disease
Shoji, M., Matsubara, E., Kanai, M., Watanabe, M., Nakamura, T., Tomidokoro, Y., Shizuka, M., Wakabayashi, K., Igeta, Y., Ikeda, Y., et al. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00122-1 · Cited by 221
Nicotine Inhibits Amyloid Formation by the β-Peptide
Salomon, A. R., Marcinowski, K. J., Friedland, R. P., & Zagorski, M. G. (1996) · Biochemistry · doi:10.1021/bi9617264 · Cited by 220
β-Amyloid Regulation of Presynaptic Nicotinic Receptors in Rat Hippocampus and Neocortex
Dougherty, J. J., Wu, J., & Nichols, R. A. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-17-06740.2003 · Cited by 213
The Toxicity of the Alzheimer's β-Amyloid Peptide Correlates with a Distinct Fiber Morphology
Seilheimer, B., Bohrmann, B., Bondolfi, L., Müller, F., Stüber, D., & Döbeli, H. (1997) · Journal of Structural Biology · doi:10.1006/jsbi.1997.3859 · Cited by 207
Ion Channel Formation by Amyloid-β42 Oligomers but Not Amyloid-β40 in Cellular Membranes
Bode, D. C., Baker, M. D., & Viles, J. H. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.762526 · Cited by 210
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Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex
Rees, T. M. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00230-0 · Cited by 212
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“To gain an insight into the mechanism of the increase in infarct size in APP transgenics, we measured Ab concentration in the postischemic brain using a sensitive ELISA-based assay (Suzuki et al., 1994; Gravina et al., 1995).”
MethodSelf-citationAβ-peptides enhance vasoconstriction in cerebral circulation
Niwa, K., Porter, V. A., Kazama, K., Cornfield, D., Carlson, G. A., & Iadecola, C. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.6.h2417 · Cited by 202
Deciphering the genesis and fate of amyloid β-protein yields novel therapies for Alzheimer disease
Selkoe, D. J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci16783 · Cited by 230
Harigaya, Y., Saido, T. C., Eckman, C. B., Prada, C.-M., Shoji, M., & Younkin, S. G. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3490 · Cited by 202
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Sporadic and Familial Cerebral Amyloid Angiopathies
Révész, T., Holton, J. L., Lashley, T., Plant, G. T., Rostagno, A. A., Ghiso, J. A., & Frangione, B. (2002) · Brain Pathology · doi:10.1111/j.1750-3639.2002.tb00449.x · Cited by 204
“below), A 42 is also deposited (11, 39, 53, 78, 101) with higher A 42 to A 40 ratios in cortical than in leptomeningeal vessels (101) (Figure 1 B-D).”
BackgroundCharacterization of the Interactions of Alzheimer β‐Amyloid Peptides with Phospholipid Membranes
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Treatment for Rheumatoid Arthritis and Risk of Alzheimer’s Disease: A Nested Case-Control Analysis
Chou, R. C., Kane, M., Ghimire, S., Gautam, S., & Gui, J. (2016) · CNS Drugs · doi:10.1007/s40263-016-0374-z · Cited by 194
Molecular Dynamics Simulation of Amyloid β Dimer Formation
Urbanc, B., Cruz, L., Ding, F., Sammond, D. W., Khare, S. D., Buldyrev, S. V., Stanley, E., & Dokholyan, N. V. (2004) · Biophysical Journal · doi:10.1529/biophysj.104.040980 · Cited by 194
The Cerebral β-Amyloid Angiopathies: Hereditary and Sporadic
Zhang-Nunes, S., Maat–Schieman, M. L. C., van Duinen, S. G., Roos, R. A. C., Frosch, M. P., & Greenberg, S. M. (2006) · Brain Pathology · doi:10.1111/j.1750-3639.2006.tb00559.x · Cited by 202
Frydman‐Marom, A., Levin, A., Farfara, D., Benromano, T., Scherzer‐Attali, R., Peled, S., Vassar, R. J., Segal, D., Gazit, E., Frenkel, D., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016564 · Cited by 197
Metadata
- Authors
- Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G.
- Affiliations
- Case Western Reserve University (US)
- Takeda (Japan) (JP)
- Corresponding author
- Younkin, Steven G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-03
- Volume
- 270
- Issue
- 13
- Pages
- 7013-7016
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1618236677
- Cited by
- 676
- References
- 20
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 19 · 2023: 21 · 2022: 23 · 2021: 33 · 2020: 33 · 2019: 22 · 2018: 18 · 2017: 22 · 2016: 27 · 2015: 20 · 2014: 22 · 2013: 24 · 2012: 24
- FWCI
- 17.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag012685-04)
- National Institute on Aging (AG06656, R01AG006656, AG12685)
- 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-beta 42, Aβ40, cerebral amyloid angiopathy, amyloid plaques, cerebral cortex, vascular wall, amyloid deposition, cerebrospinal fluid
- MeSH terms
- Alzheimer Disease, Cerebral Cortex, Chromatography, Gel, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Reference Values, Temporal Lobe, Amyloid beta-Peptides
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