CSF synaptic biomarkers in the preclinical stage of Alzheimer’s disease and their association with MRI and PET markers of neurodegeneration: a cross-sectional study

Objective: To determine whether CSF synaptic biomarkers are altered in the early preclinical stage of the Alzheimer’s continuum and associated with Alzheimer’s disease (AD) risk factors, primary pathology, and neurodegeneration markers.

Methods: Cross-sectional study in the ALFA+ cohort, comprising middle-aged cognitively unimpaired participants. CSF neurogranin and GAP-43 were measured using immunoassays and SNAP-25 and synaptotagmin-1 using immunoprecipitation mass spectrometry. AD CSF biomarkers Aβ42/40, p-tau and t-tau, and the neurodegeneration biomarker NfL were also measured. Participants underwent structural MRI, and fluorodeoxyglucose and Aβ PET imaging. General linear modeling was used to test the associations between CSF synaptic biomarkers and risk factors, Aβ pathology, tau pathology, and neurodegeneration markers.

Results: All CSF synaptic biomarkers increased with age. CSF neurogranin was higher in females, while CSF SNAP-25 was higher in APOE-ε4 carriers. All CSF s...