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APOE epsilon 4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease

Sun, X; Dong, C; Levin, B; Crocco, E; Loewenstein, D; Zetterberg, H; Blennow, K; (2016) APOE epsilon 4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease. Alzheimer's & Dementia , 12 (11) pp. 1159-1166. 10.1016/j.jalz.2016.05.003. Green open access

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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.

Type: Article
Title: APOE epsilon 4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jalz.2016.05.003
Publisher version: http://doi.org/10.1016/j.jalz.2016.05.003
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Synaptic function; Neurogranin; APOE ε4; Alzheimer's disease; APOE; Mild cognitive impairment
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1538021
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