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Title: Perivascular spaces are associated with tau pathophysiology and synaptic dysfunction in early Alzheimer’s continuum
Author: Vilor Tejedor, Natalia
Ciampa, Iacopo
Operto, Grégory
Falcón, Carles
Suárez Calvet, Marc
Crous Bou, Marta
Shekari, Mahnaz
Arenaza Urquijo, Eider M.
Milà Alomà, Marta
Grau Rivera, Oriol
Minguillón Gil, Carolina
Kollmorgen, Gwendlyn
Zetterberg, Henrik
Blennow, Kaj
Guigo, Roderic
Molinuevo, José Luis
Gispert, Juan Domingo
Beteta, Annabella
Brugulat Serrat, Anna
Cacciaglia, Raffaele
Cañas, Alba
Deulofeu, Carme
Cumplido, Irene
Dominguez, Ruth
Emilio, Maria
Fauria, Karine
Fuentes, Sherezade
Hernandez, Laura
Huesa, Gema
Huguet, Jordi
Marne, Paula
Menchón, Tania
Polo, Albina
Pradas, Sandra
Rodríguez Fernández, Blanca
Sala Vila, Aleix
Sánchez Benavides, Gonzalo
Salvadó, Gemma
Soteras, Anna
Vilanova, Marc
For The Alfa Study
Keywords: Líquid cefalorraquidi
Malaltia d'Alzheimer
Cerebrospinal fluid
Alzheimer's disease
Issue Date: 5-Aug-2021
Publisher: Springer Science and Business Media LLC
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 < 0.071). Results: The degree of PVS significantly increased with age in both, BG and CS regions independently of cardiovascular risk factors. Higher levels of p-tau, t-tau, and neurogranin were significantly associated with ePVS in the CS of Aβ positive individuals, after accounting for relevant confounders. No associations were detected in the BG neither in Aβ negative participants. Conclusions: Our results support that ePVS in the CS are specifically associated with tau pathophysiology, neurodegeneration, and synaptic dysfunction in asymptomatic stages of the Alzheimer's continuum.
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It is part of: Alzheimer's Research & Therapy, 2021, vol. 13
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ISSN: 1758-9193
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Publicacions de projectes de recerca finançats per la UE

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