We previously noted that some aged human cortical specimens containing very low or negligible levels of amyloid beta-protein (As) by enzyme immunoassay (EIA) provided prominent signals at 6 approximately 8 kd on the Western blot, probably representing sodium dodecyl sulfate (SDS)-stable Abeta dimer. Re-examination of the specificity of the EIA revealed that BAN50- and BNT77-based EIA, most commonly used for the quantitation of Abeta, capture SDS-dissociable Abeta but not SDS-stable Abeta dimer. Thus, all cortical specimens in which the levels of Abeta were below the detection limits of EIA were subjected to Western blot analysis. A fraction of such specimens contained SDS-stable dimer at 6 approximately 8 kd, but not SDS-dissociable A(beta) monomer at approximately 4 kd, as judged from the blot. This A(beta) dimer is unlikely to be generated after death, because (i) specimens with very short postmortem delay contained the A(beta) dimer, and (ii) until 12 hours postmortem, such SDS-stable A(beta) dimer is detected only faintly in PDAPP transgenic mice. The presence of A(beta) dimer in the cortex may characterize the accumulation of A(beta) in the human brain, which takes much longer than that in PDAPP transgenic mice.
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http://dx.doi.org/10.1016/s0002-9440(10)65273-x | DOI Listing |
J Am Chem Soc
January 2025
Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
Our recent molecular dynamics simulations of decomposing Alzheimer's disease plaques, under oscillating- and static external electric fields (Os-EEFs and St-EEFs), revealed the superiority of Os-EEF for decomposing plaques consisting of the 7-residue peptide segment. This conclusion is now reinforced by studying the dimers of the short peptides and trimers of the full-length Aβ-42 peptide. Thus, the dispersed peptides obtained following St-EEF applications reformed the plaques once the St-EEF subsided.
View Article and Find Full Text PDFJ Phys Chem B
December 2024
Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi, Sakyo-ku, Kyoto 606-8501, Japan.
A parallel dimeric Aβ(1-40) peptide was prepared, and its structural and fibrillogenic characteristics were examined. The covalent linking of the peptide strongly facilitated the spontaneous formation of thioflavin-T-active, fibrillar aggregates rich in β strands without a lag phase. However, the aggregates formed by the dimeric peptide did not exhibit "seeding activity" to catalyze the formation of amyloid fibrils by wild-type Aβ(1-40) molecules.
View Article and Find Full Text PDFJ Phys Chem B
November 2024
Laboratory of Biophysics, Institute for Advanced Study in Technology, Ton Duc Thang University, Ho Chi Minh City 72915, Vietnam.
Advances in Alzheimer's disease (AD) are related to the oligomerization of Amyloid β (Aβ) peptides. Therefore, alteration of the process can prevent AD. We investigated the Aβ dimerization under the effects of gold nanoparticles using temperature replica-exchange molecular dynamics (REMD) simulations.
View Article and Find Full Text PDFChem Commun (Camb)
November 2024
Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
The aggregation of amyloid-β (Aβ) peptides, particularly Aβ, plays a key role in Alzheimer's disease pathogenesis. In this study, we investigate how dimerisation transforms the free energy surface (FES) of the Aβ monomer when it interacts with another Aβ peptide. We find that the monomer FES is a structurally inverted funnel with a disordered state at the global minimum.
View Article and Find Full Text PDFMol Neurobiol
October 2024
Chemistry Department and Coimbra Chemistry Centre - Institute of Molecular Sciences (CQC-IMS), University of Coimbra, 3004-535, Coimbra, Portugal.
Alzheimer's disease (AD) is the most common form of dementia around the world (~ 65%). Here, we portray the neuropathology of AD, biomarkers, and classification of amyloid plaques (diffuse, non-cored, dense core, compact). Tau pathology and its involvement with Aβ plaques and cell death are discussed.
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