Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer’s continuum

Autor: Natalia Vilor-Tejedor, Iacopo Ciampa, Grégory Operto, Carles Falcón, Marc Suárez-Calvet, Marta Crous-Bou, Mahnaz Shekari, Eider M. Arenaza-Urquijo, Marta Milà-Alomà, Oriol Grau-Rivera, Carolina Minguillon, Gwendlyn Kollmorgen, Henrik Zetterberg, Kaj Blennow, Roderic Guigo, José Luis Molinuevo, Juan Domingo Gispert, for the ALFA study
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-13 (2021)
Druh dokumentu: article
ISSN: 1758-9193
DOI: 10.1186/s13195-021-00878-5
Popis: Abstract Background Perivascular spaces (PVS) have an important role in the elimination of metabolic waste from the brain. It has been hypothesized that the enlargement of PVS (ePVS) could be affected by pathophysiological mechanisms involved in Alzheimer’s disease (AD), such as abnormal levels of CSF biomarkers. However, the relationship between ePVS and these pathophysiological mechanisms remains unknown. Objective We aimed to investigate the association between ePVS and CSF biomarkers of several pathophysiological mechanisms for AD. We hypothesized that ePVS will be associated to CSF biomarkers early in the AD continuum (i.e., amyloid positive cognitively unimpaired individuals). Besides, we explored associations between ePVS and demographic and cardiovascular risk factors. Methods The study included 322 middle-aged cognitively unimpaired participants from the ALFA + study, many within the Alzheimer’s continuum. NeuroToolKit and Elecsys® immunoassays were used to measure CSF Aβ42, Aβ40, p-tau and t-tau, NfL, neurogranin, TREM2, YKL40, GFAP, IL6, S100, and α-synuclein. PVS in the basal ganglia (BG) and centrum semiovale (CS) were assessed based on a validated 4-point visual rating scale. Odds ratios were calculated for associations of cardiovascular and AD risk factors with ePVS using logistic and multinomial models adjusted for relevant confounders. Models were stratified by Aβ status (positivity defined as Aβ42/40
Databáze: Directory of Open Access Journals
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