EPND cohort of 353 participants: CSF proteins that differ in Alzheimer's, Lewy body dementia and Parkinson's
A European consortium assembled a harmonized cohort of 353 people with three neurodegenerative diseases and controls. An exploratory CSF analysis found disease-specific and shared altered proteins.
A European consortium has described the design of the European Platform for Neurodegenerative Diseases (EPND) cohort and reported an exploratory analysis of cerebrospinal fluid (CSF) proteins in it. The work was published in «Alzheimer s Research & Therapy» biomedcentral.com
Alzheimer s Research & Therapybiomedcentral.comOpen source ↗. The cohort covers Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease (PD).
The authors note that treatment development is hampered by limited understanding of disease-specific and shared mechanisms. Cohorts with harmonized in vivo biomarkers for all three diseases are scarce, which limits comparisons between them.
Cohort design and measurements
Participants were selected from ten European cohorts. The EPND cohort includes 353 people, mean age 67.1 years (SD 9.2), 133 of them (38%) women. There are 151 people with AD, 67 with DLB, 75 with PD, 57 controls and 3 with other diagnoses.
Samples were analysed centrally. Amyloid-β 42, amyloid-β 40, phosphorylated tau 181 and neurofilament light were measured in CSF and plasma, and total α-synuclein in CSF, all with Elecsys assays. Complement was assessed in CSF (Milliplex) and plasma (SVAR). CSF proteomics panels were Olink Explore 3072 and SomaScan 7k biomedcentral.com
Alzheimer s Research & Therapybiomedcentral.comOpen source ↗.
Data on demographics, clinical status, cognition, rating scales, lifestyle, genetics and key imaging measures were harmonized centrally. Analyses and harmonization produced five datasets, which can be requested for research reuse through the EPND Catalogue.
Dysregulated CSF proteins
The exploratory analysis covered a subset of 325 participants and 1,617 CSF proteins measured by Olink proximity extension assays. Linear regression was adjusted for age, sex and mean CSF protein level, and p-values were FDR-corrected.
Proteins specifically dysregulated were found in AD (9), DLB (1) and PD (2). Ten proteins were similarly dysregulated in AD and DLB, and four in DLB and PD. No shared proteins were found between AD and PD biomedcentral.com
Alzheimer s Research & Therapybiomedcentral.comOpen source ↗.
The authors state that the cohort supports collaborative studies across neurodegenerative diseases, and that current and future results may inform understanding of disease mechanisms and trial design.
