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

Xiaoyan Sun, Chuanhui Dong, Bonnie Levin, Elizabeth Crocco, David Loewenstein, Henrik Zetterberg, Kaj Blennow, Clinton B Wright

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - 2016

Fingerprint

Neurogranin
Apolipoprotein E4
Alzheimer Disease
tau Proteins
Cognition
Protein Isoforms
Biomarkers
Education

Keywords

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

ASJC Scopus subject areas

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

Cite this

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title = "APOE ε4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease",
abstract = "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.",
keywords = "Alzheimer's disease, APOE, APOE ε4, Mild cognitive impairment, Neurogranin, Synaptic function",
author = "Xiaoyan Sun and Chuanhui Dong and Bonnie Levin and Elizabeth Crocco and David Loewenstein and Henrik Zetterberg and Kaj Blennow and Wright, {Clinton B}",
year = "2016",
doi = "10.1016/j.jalz.2016.05.003",
language = "English (US)",
journal = "Alzheimer's and Dementia",
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T1 - APOE ε4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease

AU - Sun, Xiaoyan

AU - Dong, Chuanhui

AU - Levin, Bonnie

AU - Crocco, Elizabeth

AU - Loewenstein, David

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Wright, Clinton B

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - APOE

KW - APOE ε4

KW - Mild cognitive impairment

KW - Neurogranin

KW - Synaptic function

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