Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls

Acta Neuropathol. 2014 May;127(5):633-43. doi: 10.1007/s00401-014-1266-2. Epub 2014 Mar 15.


The apolipoprotein E (ApoE) ε4 allele is the strongest risk factor of sporadic Alzheimer's disease (AD), however, the fluid concentrations of ApoE and its different isoforms (ApoE2, ApoE3 and ApoE4) in AD patients and among APOE genotypes (APOE ε2, ε3, ε4) remain controversial. Using a novel mass spectrometry-based method, we quantified total ApoE and specific ApoE isoform concentrations and potential associations with age, cognitive status, cholesterol levels and established AD biomarkers in cerebrospinal fluid (CSF) from AD patients versus non-AD individuals with different APOE genotypes. We also investigated plasma total ApoE and ApoE isoform composition in a subset of these individuals. In total n = 43 AD and n = 43 non-AD subjects were included. We found that CSF and plasma total ApoE levels did not correlate with age or cognitive status and did not differ between AD and non-AD subjects deeming ApoE as an unfit diagnostic marker for AD. Also, whereas CSF ApoE levels did not vary between APOE genotypes APOE ε4 carriers exhibited significantly decreased plasma ApoE levels attributed to a specific decrease in the ApoE4 isoform concentrations. CSF total ApoE concentrations were positively associated with CSF, total tau, tau phosphorylated at Thr181 and Aβ1-42 of which the latter association was weaker and only present in APOE ε4 carriers indicating a differential involvement of ApoE in tau versus Aβ-linked neuropathological processes. Future studies need to elucidate whether the observed plasma ApoE4 deficiency is a life-long condition in APOE ɛ4 carriers and whether this decrease in plasma ApoE predisposes APOE ɛ4 carriers to AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoprotein E2 / blood
  • Apolipoprotein E2 / cerebrospinal fluid
  • Apolipoprotein E2 / genetics
  • Apolipoprotein E3 / blood
  • Apolipoprotein E3 / cerebrospinal fluid
  • Apolipoprotein E3 / genetics
  • Apolipoprotein E4 / blood
  • Apolipoprotein E4 / cerebrospinal fluid
  • Apolipoprotein E4 / genetics
  • Apolipoproteins E / blood*
  • Apolipoproteins E / cerebrospinal fluid*
  • Apolipoproteins E / genetics
  • Biomarkers / cerebrospinal fluid
  • Cholesterol / blood
  • Cholesterol / cerebrospinal fluid
  • Cognition
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid
  • Phosphorylation
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Apolipoprotein E2
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoproteins E
  • Biomarkers
  • MAPT protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins
  • Cholesterol