Glymphatic system clearance and Alzheimer's disease risk: a CSF proteome-wide study

• Published in: Alzheimer's research & therapy 2025-01, Vol.17 (1), p.31-13, Article 31
• Main Authors: Cullell, Natalia, Caruana, Giovanni, Elias-Mas, Andrea, Delgado-Sanchez, Ariane, Artero, Cristina, Buongiorno, Maria Teresa, Almería, Marta, Ray, Nicola J, Correa, Sonia A L, Krupinski, Jerzy
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - cerebrospinal fluid; Alzheimer's disease; Analysis; Biomarkers - cerebrospinal fluid; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Cerebrospinal fluid; Cognitive Dysfunction - cerebrospinal fluid; Cohort Studies; Development and progression; Female; Glymphatic System; Health aspects; Humans; Inflammation; Magnetic Resonance Imaging; Male; Middle Aged; Mild cognitive impairment; MRI; Proteome - metabolism; Proteomics; Proteomics - methods; Risk factors
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-024-01612-7

The emerging evidence of the role of the glymphatic system (GS) in Alzheimer's disease (AD) provides new opportunities for intervention from the earliest stages of the disease. The aim of the study is to evaluate the efficacy of GS in AD to identify new disease biomarkers. We performed a two-stage proteomic study to evaluate the GS health using intravenous gadolinium-based contrast agent (GBCA) with serial T1 3T magnetic resonance imaging (MRI) in individuals with amnestic mild cognitive impairment (aMCI). In Stage 1 (evaluated in the Cohort 1 of aMCI participants (n = 11)), we correlated the levels of 7K cerebrospinal fluid (CSF) proteins (estimated by SOMAscan) with GS health in 78 Freesurfer-segmented brain regions of interest (ROIs). A total of seven different proteins were significantly associated with GS health (p-value