Student and Faculty Publications
Publication Date
8-3-2023
Journal
EMBO Reports
Abstract
Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, tropism to specific brain regions, differential recruitment of Aβ40 /Aβ42 peptides, and induction of microglial and astroglial responses. Importantly, the aggregates induced by 2F and 3F are structurally different as determined by ssNMR. Our study analyzes the biological properties of purified Aβ polymorphs that have been characterized at the atomic resolution level and provides relevant information on the pathological significance of misfolded Aβ strains.
Keywords
Mice, Animals, Amyloid beta-Peptides, Alzheimer Disease, Mice, Transgenic, Plaque, Amyloid, Proteolysis, amyloid‐beta, animal models, prion, protein conformation, strains, Molecular Biology of Disease, Neuroscience, Structural Biology
Included in
Animals Commons, Bioinformatics Commons, Biology Commons, Biomedical Informatics Commons, Medical Microbiology Commons, Medical Pathology Commons, Neurosciences Commons, Oncology Commons, Pathological Conditions, Signs and Symptoms Commons
Comments
Supplementary Materials
Data Availability Statement
PMID: 37424505