APOE ε4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease

Alzheimer's Disease Neuroimaging Initiative

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Introduction Pathogenesis of Alzheimer's disease (AD) in apolipoprotein E ε4 (APOE ε4) carriers remains unclear. We hypothesize that APOE isoforms have differential effects on synaptic function. Methods We compared levels of CSF neurogranin (Ng) between APOE ε4 carriers and noncarriers in 399 subjects with normal cognition, mild cognitive impairment (MCI), and AD. We examined associations between Ng levels and age, education, gender, CSF-Aβ42, and tau protein. Results Neurogranin levels were significantly higher in APOE ε4 carriers compared to APOE ε4 noncarriers with MCI. Levels of Ng between the APOE ε4 carriers and APOE ε4 noncarriers with AD did not differ. Ng levels were correlated with MMSE and levels of tau and Aβ42. Discussion Significantly higher CSF Ng levels in APOE ε4 carriers with MCI may reflect synaptic injury underlying early cognitive impairment. Neurogranin may be an early biomarker of AD and important for disease diagnosis and timing of intervention in APOE ε4 carriers.

Original languageEnglish (US)
Pages (from-to)1159-1166
Number of pages8
JournalAlzheimer's and Dementia
Issue number11
StatePublished - Nov 1 2016


  • APOE
  • APOE ε4
  • Alzheimer's disease
  • Mild cognitive impairment
  • Neurogranin
  • Synaptic function

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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