Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer's disease

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Citações na Scopus
10
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
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Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PORTFOLIO
Autores
JOHNSON, Erik C. B.
BIAN, Shijia
HAQUE, Rafi U.
CARTER, E. Kathleen
WATSON, Caroline M.
GORDON, Brian A.
PING, Lingyan
DUONG, Duc M.
EPSTEIN, Michael P.
MCDADE, Eric
Citação
NATURE MEDICINE, v.29, n.8, p.1979-+, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Alzheimer's disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes-aggregation of the amyloid-& beta; (A & beta;) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)-are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of A & beta; plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with A & beta; plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than A & beta; and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with A & beta; and tau. Proteomic analysis of cerebrospinal fluid from individuals with autosomal dominant Alzheimer's disease reveals how this complex and chronic disease evolves over many decades.
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URI
https://observatorio.fm.usp.br/handle/OPI/59205
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Coleções
Artigos e Materiais de Revistas Científicas - HC/ICHC