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



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.



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.



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.
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.
Xiaoyan
X
Sun
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.
Chuanhui
C
Dong
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.
Bonnie
B
Levin
Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
Elizabeth
E
Crocco
Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
David
D
Loewenstein
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.
Henrik
H
Zetterberg
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.
Kaj
K
Blennow
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.
Clinton B
CB
Wright
D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid* / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004522:Educational Status; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D000073216:Mental Status and Dementia Tests; D009687:Nuclear Proteins / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D016601:RNA-Binding Proteins; D012306:Risk; D012737:Sex Factors; D013569:Synapses / Q000378:metabolism; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; C054369:MAPT protein, human; C532399:NGDN protein, human; D009687:Nuclear Proteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
APOE; APOE ε4; Alzheimer's disease; Mild cognitive impairment; Neurogranin; Synaptic function