Age-dependent decline in the apolipoprotein E level in cerebrospinal fluid from control subjects and its increase in cerebrospinal fluid from patients with Alzheimer's disease

Eur Neurol. 2000;43(3):161-9. doi: 10.1159/000008157.


In order to address the significance of apolipoprotein E (apoE) in the pathogenesis as well as the clinical diagnosis of Alzheimer's disease (AD), we measured its level in cerebrospinal fluid (CSF) from randomly selected Japanese control subjects at various ages (n = 36), which included 14 age-matched controls, and from AD patients including early-onset (n = 11, EOAD) and late-onset (n = 14, LOAD) cases. The CSF apoE level in controls linearly decreased during aging to over 80 years (r(2) = 0.323, p < 0.0001). The CSF apoE level in AD patients was 31.9% elevated compared to the age-matched controls (n = 14, p < 0.05) and linearly increased with a decrement of the patients' Mini Mental State Examination scores. Moreover, the CSF apoE level of EOAD patients (n = 11) was higher than that of LOAD patients (n = 14, p < 0.05), whose APOE epsilon4 allele frequency was significantly higher than that of controls (chi(2) = 7. 16, p < 0.03). Two-dimensional gel electrophoretic analysis of the heparin-Mn(2+)-precipitable lipoprotein fraction in CSFs showed that the ratio between the level of CSF apoA-I and that of CSF apoE of controls was significantly higher than those of all AD and LOAD subjects (p < 0.01, p < 0.05), while the CSF apoA-I-to-apoE ratios of the two AD groups were not significantly different. These results suggest that overproduction of apoE protein may be a consequence of astroglial response to neurodegeneration in AD and that the determination of CSF apoliprotein levels serves as a clinical marker for monitoring the progression of AD.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics
  • Apolipoproteins E / cerebrospinal fluid*
  • Apolipoproteins E / genetics
  • Child
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Reference Values


  • Apolipoproteins E