Apolipoprotein B is a novel marker for early tau pathology in Alzheimer's disease

Introduction We examine the role of brain apolipoprotein B (apoB) as a putative marker of early tau pathology and cognitive decline. Methods Cerebrospinal fluid (CSF) samples from cognitively normal and Alzheimer's disease (AD) participants were collected to measure protein levels of apoB and AD biomarkers amyloid beta (Aβ), t‐tau and p‐tau, as well as synaptic markers GAP43, SYNAPTOTAGMIN‐1, synaptosome associated protein 25 (SNAP‐25), and NEUROGRANIN. CSF apoB levels were contrasted with positron emission tomography (PET) scan measures of Aβ (18F‐NAV4694) and Tau (flortaucipir) along with cognitive assessment alterations over 6 to 8 years. Results CSF apoB levels were elevated in AD participants and correlated with t‐tau, p‐tau, and the four synaptic markers in pre‐symptomatic individuals. In the latter, CSF apoB levels correlated with PET flortaucipir‐binding in entorhinal, parahippocampal, and fusiform regions. Baseline CSF apoB levels were associated with longitudinal visuospatial cognitive decline. Discussion CSF apoB markedly associates with early tau dysregulation in asymptomatic subjects and identifies at‐risk individuals predisposed to develop visuospatial cognitive decline over time.