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

Alzheimers Dement. 2022 May;18(5):875-887. doi: 10.1002/alz.12442. Epub 2021 Sep 29.


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.

Keywords: Alzheimer's disease; PET scans; RBANS; apolipoprotein B; cerebrospinal fluid; synaptic markers; tau pathology.

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Apolipoprotein B-100
  • Apolipoproteins
  • Apolipoproteins B
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction* / metabolism
  • Humans
  • Positron-Emission Tomography / methods
  • tau Proteins / cerebrospinal fluid


  • APOB protein, human
  • Amyloid beta-Peptides
  • Apolipoprotein B-100
  • Apolipoproteins
  • Apolipoproteins B
  • Biomarkers
  • tau Proteins