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

Introduction: Pathogenesis of Alzheimer's disease (AD) in apolipoprotein E epsilon 4 (APOE epsilon 4) carriers remains unclear. We hypothesize that APOE isoforms have differential effects on synaptic function. Methods: We compared levels of CSF neurogranin (Ng) between APOE epsilon 4 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-A beta 42, and tau protein. Results: Neurogranin levels were significantly higher in APOE epsilon 4 carriers compared to APOE epsilon 4 noncarriers with MCI. Levels of Ng between the APOE epsilon 4 carriers and APOE 64 noncarriers with AD did not differ. Ng levels were correlated with MMSE and levels of tau and A beta 42. Discussion: Significantly higher CSF Ng levels in APOE epsilon 4 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 epsilon 4 carriers. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.