Amyloid pathology arrangements in Alzheimer’s disease brains modulate in vivo seeding capability
Year: 2021
Type: article
Abstract: Amyloid-β (Aβ) misfolding is one of the hallmark pathological features of Alzheimer's disease (AD). AD can manifest with diverse symptomatology including variable rates of cognitive decline, duration of clinical disease, and other detrimental changes. Several reports suggest that conformational diversity in misfolded Aβ is a leading factor for clinical variability in AD, analogous to what it has been described for prion strains in prion diseases. Notably, prion strains generate diverse patterns of misfolded protein deposition in the brains of affected individuals. Here, we tested the in vivo prion-like transmission features of four AD brains displaying particular patterns of amyloidosis. AD brains induced different phenotypes in recipient mice, as evaluated by their specific seeding activity, as well as the total amount of Aβ deposited surrounding vascular structures and the reactivity of amyloid pathology to thioflavin S. Our results support the notion that AD-subtypes are encoded in disease-associated Aβ. Further research exploring whether AD include a spectrum of different clinical conditions or syndromes may pave the way to personalized diagnosis and treatments.
Institutions: Universidad de Los Andes, Chile, Adolfo Ibáñez University, The University of Texas Health Science Center at Houston, Universidad Bernardo O'Higgins, Biomedical Research Networking Center on Neurodegenerative Diseases, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,170
Funders: Alzheimer's Association, National Alliance for Research on Schizophrenia and Depression, Ministerio de Ciencia y Tecnología, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España, Agencia Nacional de Investigación y Desarrollo, National Institutes of Health, National Institute on Aging, Fondo de Fomento al Desarrollo Científico y Tecnológico
Awards: Isolation, characterization and pathogenic role of self-propagating conformational amyloid-beta strains, Role of circulating Abeta seeds and peripheral tissue damage in Alzheimer's disease pathogenesis, Characterization of Natural and Synthetic Aß “Conformational Strains”, Misfolded Protein Aggregates in HIV infection, G3585329184, G4961754223, G5492199721, MACHINE LEARNING PARA EL DIAGNOSTICO PRECOZ Y PERFIL MULTIMODAL DE LA ENFERMEDAD DE ALZHEIMER BASADO EN MIRNA DE EXOSOMAS CIRCULANTES., G6291921393, G6405761789, CONTRIBUTION OF PERIPHERAL TAU AGGREGATES TO ALZHEIMER´S DISEASE PATHOGENESIS, G7616641907, Infection-driven mechanisms associated with Alzheimer's disease pathology, G9000026023, G9000060959, Research Resource for Human Organs and Tissues, G949726097
OpenAlex ID: W3142780846