Beta Amyloid 1-43: Abeta 1-43:Amyloid Beta Peptide:1-43: Beta Amyloid Peptides 1-43: Research Paper of Abeta Peptide 1-43

Research Papers on beta amyloid 1-43

Title:
Amyloid beta protein (A beta) in Alzheimer's disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43)

Authors:
Gravina SA, Ho L, Eckman CB, Long KE, Otvos L Jr, Younkin LH, Suzuki N, Younkin SG.



Abstract:
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.


Title:
Amyloid beta protein (A beta) deposition: A beta 42(43) precedes A beta 40 in Down syndrome.

Authors:
Iwatsubo T, Mann DM, Odaka A, Suzuki N, Ihara Y.

Abstract:
The chronological relationship regarding deposition of amyloid beta protein (A beta) species, A beta 40 and A beta 42(43), was investigated in 16 brains from Down syndrome patients aged 31 to 64 years. The frontal cortex was probed with two end-specific monoclonals that recognize A beta 40 or A beta 42(43). All senile plaques detected with an authentic beta monoclonal were also A beta 42(43) positive, but only a varying proportion was A beta 40 positive. In young (< or = 50 years old) brains there were many A beta 42(43)-positive, A beta 40-negative diffuse plaques, but only few A beta 40-positive senile plaques (mean, 6.3% of total number of senile plaques). The 2 youngest Down syndrome brains showed only diffuse plaques that were all A beta 42(43) positive but A beta 40 negative. Old (> 50 years old) brains contained many mature senile plaques with amyloid cores in addition to diffuse and immature plaques and the proportion of A beta 40-positive senile plaques was increased (mean, 42% of total). Cerebral amyloid angiopathy was more abundant in old Down syndrome brains and was positive for both A beta 40 and A beta 42(43). In cerebral amyloid angiopathy, A beta 40 predominated over A beta 42(43) in both staining intensity and number of positive vessels. These results indicate that (1) the A beta species initially deposited in the brain as senile plaques is A beta 42(43) and A beta 40 only appears a decade later, and (2) in cerebral amyloid angiopathy A beta 40 appears as early as A beta 42(43).

Title:
Effects of beta-amyloid peptides on the fluidity of membranes from frontal and parietal lobes of human brain. High potencies of A beta 1-42 and A beta 1-43.

Authors:
Müller WE, Eckert GP, Scheuer K, Cairns NJ, Maras A, Gattaz WF.

Abstract:
Beta-amyloid peptide (A beta) and several A beta-fragments decrease the fluidity of human cortex membranes in a concentration dependent fashion. The effect of A beta on membrane fluidity increases with peptide length, is most pronounced for A beta 1-43 and can be seen at concentrations as low as 100 nmol/l. While the fragment A beta 25-35 is active, scrambled peptide (A beta 35-25) when investigated under similar conditions shows no effects on membrane fluidity. The effect of A beta peptides on fluidity of the phospholipid bilayer is more pronounced in the hydrocarbon core (labeled with the fluorescence probe 1,6-diphenylhexa-1,3,5-triene) than in the region of the hydrophilic heads (labeled with the fluorescence probe 1-[4'-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene). It is suggested that the effect of A beta on neuronal membranes is probably a major initial mechanism in a cascade of events finally leading to neurotoxicity and cell death in Alzheimer's disease.

Title:
Predominant deposition of amyloid-beta 42(43) in plaques in cases of Alzheimer's disease and hereditary cerebral hemorrhage associated with mutations in the amyloid precursor protein gene

Authors:
DM Mann, T Iwatsubo, Y Ihara, NJ Cairns, PL Lantos, N Bogdanovic, L Lannfelt, B Winblad, ML Maat-Schieman and MN Rossor

Abstract:
Amyloid (A beta) deposition was investigated in cases of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis, Dutch type, due to mutations in the amyloid precursor protein (APP) gene using the end-specific monoclonal antibodies BA27 and BC05 that recognize A beta 40 or A beta 42(43), respectively. In cases of APP717 mutation the predominant A beta species within plaques terminate at A beta 42(43) with relatively little A beta 40 being present. The total amount of A beta deposited as A beta 42(43) is significantly greater than in sporadic Alzheimer's disease, consistent with the suggestion that this mutation might influence the processing of APP so as to produce more of the highly aggregatable form, A beta 1-42. In cases of APP670/671 mutation the major peptide in plaques is also A beta 42(43), although the proportion of plaques containing A beta 40, and the total A beta load is similar to that in sporadic Alzheimer's disease. As in sporadic Alzheimer's disease, the vascular amyloid in APP670/671 and APP717 and in cases of hereditary cerebral hemorrhage with amyloidosis, Dutch type is predominantly A beta 40 in this latter disorder, however, parenchymal deposits are exclusively A beta 42(43). Although the various APP mutations may influence the type, quantity, and location of A beta deposited, the predominant, and possibly the initial, species deposited in the brain parenchyma is A beta 42(43).

Title:
Amyloid beta protein (Abeta) deposition in chromosome 14-linked Alzheimer's disease: predominance of Abeta42(43).

Authors:
Mann DM, Iwatsubo T, Cairns NJ, Lantos PL, Nochlin D, Sumi SM, Bird TD, Poorkaj P, Hardy J, Hutton M, Prihar G, Crook R, Rossor MN, Haltia M.

Abstract:
Amyloid beta protein (Abeta) deposition was investigated in the frontal cortex of 8 cases of (genetically confirmed) chromosome 14-linked Alzheimer's disease (AD) using the end-specific monoclonal antibodies BA27 and BC05 to detect the presence of Abeta40 and Abeta42(43), respectively. In all patients, Abeta42(43) was the predominant peptide species present. The total amount of Abeta40 and Abeta42(43) deposited was more than twice the amount deposited in cases of sporadic AD of similar disease duration, although the ratio between the extent of Abeta40 and Abeta42(43) deposition was unaltered, compared with sporadic AD. Therefore, (one of) the effects of the mutations in the presenilin 1:PS-1 (S182) gene may be to cause or at least promote an early and excessive deposition of Abeta42(43) within the brain, a property shared with other inherited forms of AD, such as those due to amyloid precursor protein mutations, and Down's syndrome (trisomy 21).



Title:
Biochemical evidence for the long-tail form (A beta 1-42/43) of amyloid beta protein as a seed molecule in cerebral deposits of Alzheimer's disease.

Authors:
Tamaoka A, Kondo T, Odaka A, Sahara N, Sawamura N, Ozawa K, Suzuki N, Shoji S, Mori H.

Abstract
We measured the amounts of total A beta, A beta 1-40 and A beta 1-42/43 in brain tissues using a newly developed ELISA assay and found that the amounts of insoluble A beta 1-42/43 and insoluble A beta 1-40 were linearly related to the amount of A beta deposits or total insoluble A beta at their lower and higher concentrations, respectively. In an experiment to characterize the A beta species in brain homogenates with buffered saline, we unexpectedly detected soluble A beta which was derived from the insoluble amyloid deposits in brain tissue, indicating reversible depolymerization of A beta from insoluble amyloid deposits. To confirm this finding, we performed 5 consecutive washes of insoluble precipitates of AD brains with buffered saline. Both species of A beta were found in all 5 supernatant fractions and their amounts were gradually decreased. The ratio of A beta 1-42/43 to A beta 1-40 was increased with the numbers of washes, indicating that A beta 1-40 existed in an exposed manner as compared to A beta 1-42/43. Thus the present finding is the first biochemical evidence that A beta 1-40 was the predominant species involved in the reversible exchanging reaction on seeding A beta 1-42/43 between the soluble and the insoluble forms (amyloid fibrils).

Source: PubMed