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; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.jalz.2016.05.003

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

Alzheimers Dement. 2016 Nov;12(11):1159-1166. doi: 10.1016/j.jalz.2016.05.003. Epub 2016 Jun 16.

Authors

Xiaoyan Sun¹, Chuanhui Dong², Bonnie Levin², Elizabeth Crocco³, David Loewenstein³, Henrik Zetterberg⁴, Kaj Blennow⁵, Clinton B Wright²; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA; Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: XXS356@med.miami.edu.
² Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA; Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
³ Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University Gothenburg, Molndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory Sahlgrenska University Hospital, Mölndal, Sweden.
⁵ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University Gothenburg, Molndal, Sweden; Clinical Neurochemistry Laboratory Sahlgrenska University Hospital, Mölndal, Sweden.

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: APOE; APOE ε4; Alzheimer's disease; Mild cognitive impairment; Neurogranin; Synaptic function.

MeSH terms

Age Factors
Aged
Alzheimer Disease / cerebrospinal fluid
Alzheimer Disease / genetics
Amyloid beta-Peptides / cerebrospinal fluid
Apolipoprotein E4 / genetics*
Biomarkers / cerebrospinal fluid
Cognitive Dysfunction / cerebrospinal fluid*
Cognitive Dysfunction / genetics*
Cohort Studies
Cross-Sectional Studies
Disease Progression
Educational Status
Female
Heterozygote
Humans
Male
Mental Status and Dementia Tests
Nuclear Proteins / cerebrospinal fluid*
Peptide Fragments / cerebrospinal fluid
RNA-Binding Proteins
Risk
Sex Factors
Synapses / metabolism
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
Apolipoprotein E4
Biomarkers
MAPT protein, human
NGDN protein, human
Nuclear Proteins
Peptide Fragments
RNA-Binding Proteins
amyloid beta-protein (1-42)
tau Proteins

Abstract

MeSH terms

Substances

Grants and funding