Effects of APOE ε4 on neuroimaging, cerebrospinal fluid biomarkers, and cognition in prodromal Alzheimer's disease

Research output: Contribution to journalArticle

Abstract

Apolipoprotein (APOE) ε4 is a major genetic risk factor for Alzheimer's disease (AD), but its importance for the clinical and biological heterogeneity in AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD patients (44 APOE ε4-negative and 107 APOE ε4-positive) from the BioFINDER study. We tested cognition, 18F-flutemetamol β-amyloid (Aβ) positron emission tomography, cerebrospinal fluid biomarkers of Aβ tau and neurodegeneration, and magnetic resonance imaging of white matter pathology and brain structure. Despite having similar cortical Aβ-load and baseline global cognition (mini mental state examination), APOE ε4-negative prodromal AD had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of Aβ-peptides and neuronal injury biomarkers, more white matter pathology, more cortical atrophy, and faster decline of mini mental state examination, compared to APOE ε4-positive prodromal AD. The absence of APOE ε4 is associated with an atypical phenotype of prodromal AD. This suggests that APOE ε4 may impact both the diagnostics of AD in early stages and potentially also effects of disease-modifying treatments.

Details

Authors
Organisations
External organisations
  • University of Gothenburg
  • Veterans Health Administration
  • University of California, San Francisco
  • Sahlgrenska University Hospital
  • University College London
  • Lund University
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
  • Neurology

Keywords

  • Alzheimer's disease, APOE, Biomarkers, Cognition, Imaging, Prodromal
Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalNeurobiology of Aging
Volume71
Publication statusPublished - 2018 Nov 1
Publication categoryResearch
Peer-reviewedYes