CSF Apo-E levels associate with cognitive decline and MRI changes

Jon B. Toledo, Xiao Da, Michael W. Weiner, David A. Wolk, Sharon X. Xie, Steven E. Arnold, Christos Davatzikos, Leslie M. Shaw, John Q. Trojanowski

Research output: Contribution to journalArticlepeer-review

Abstract

Apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for Alzheimer's disease (AD) and it is thought to do so by modulating levels of its product, apolipoprotein E (Apo-E), and regulating amyloid-β (Aβ) clearance. However, information on clinical and biomarker correlates of Apo-E proteins is scarce. We examined the relationship of cerebrospinal fluid (CSF) and plasma Apo-E protein levels, and APOE genotype to cognition and AD biomarker changes in 311 AD neuroimaging initiative subjects with CSF Apo-E measurements and 565 subjects with plasma Apo-E measurements. At baseline, higher CSF Apo-E levels were associated with higher total and phosphorylated CSF tau levels. CSF Apo-E levels were associated with longitudinal cognitive decline, MCI conversion to dementia, and gray matter atrophy rate in total tau/Aβ1-42 ratio and APOE genotype-adjusted analyses. In analyses stratified by APOE genotype, our results were only significant in the group without the ε4 allele. Baseline CSF Apo-E levels did not predict longitudinal CSF Aβ or tau changes. Plasma Apo-E levels show a mild correlation with CSF Apo-E levels, but were not associated with longitudinal cognitive and MRI changes. Based on our analyses, we speculate that increased CSF Apo-E2 or -E3 levels might represent a protective response to injury in AD and may have neuroprotective effects by decreasing neuronal damage independent of tau and amyloid deposition in addition to its effects on amyloid clearance.

Original languageEnglish (US)
Pages (from-to)621-632
Number of pages12
JournalActa neuropathologica
Volume127
Issue number5
DOIs
StatePublished - May 2014

Keywords

  • APOE
  • Alzheimer's disease
  • Beta amyloid
  • Cerebrospinal fluid
  • Dementia
  • MRI
  • Neurodegeneration
  • Plasma
  • Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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