Cerebrospinal fluid VGF is associated with the onset and progression of Alzheimer's disease

BackgroundIt remains unclear whether cerebrospinal fluid (CSF) VGF (non-acronymic) is associated with the onset and progression of Alzheimer's disease (AD).ObjectiveTo assess the levels of CSF VGF throughout the AD continuum, and its association with primary AD pathology, cognition, brain atrophy, and brain metabolism.MethodsWe studied a total of 526 individuals including 377 amyloid-positive individuals (76 preclinical AD, 200 prodromal AD, and 101 AD dementia) and 149 amyloid-negative cognitively normal individuals. VGF peptide in CSF was analyzed using mass spectrometry.ResultsWe observed decreased CSF VGF in preclinical, prodromal, and AD dementia individuals than amyloid-negative cognitively normal individuals. Reduced CSF VGF was associated with cognitive decline, hippocampal atrophy, ventricle enlargement, and glucose hypometabolism at baseline, and it predicted a more marked deterioration over time.ConclusionsOur findings support the important contributions of VGF to disease pathogenesis and progression in the early stages of AD. Exploring the biologics modulating VGF might be a promising approach for AD prevention and early treatment.