Journal
ALZHEIMERS & DEMENTIA
Volume 11, Issue 10, Pages 1180-1190Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2014.10.009
Keywords
Neurogranin; Alzheimer's disease; Mass spectrometry; ELISA; Mild cognitive impairment; Prognostic marker
Categories
Funding
- Swedish Research Council [14002, K2010-63P-21562-01-4, K2011-61X-20401-05-6]
- Knut and Alice Wallenberg Foundation
- Stiftelsen Gamla Tjanarinnor
- Magnus Bergvalls Stiftelse
- Gun och Bertil Stohnes Stiftelse
- Hjarnfonden
- Alzheimer Foundation, Sweden
- Dementia Association, Sweden
- JPND Project BIOMARKAPD
- Swedish Brain Power consortium
- Alzheimer Nederland [WE. 15-2013-08]
- Torsten Soderberg Foundation
- Royal Swedish Academy of Sciences
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Introduction: Synaptic dysfunction is an early event in Alzheimer's disease (AD) pathogenesis and directly related to cognitive impairment. Consequently, synaptic biomarkers may be valuable tools for both early diagnosis and disease stage. Neurogranin (Ng) is a postsynaptic protein involved in memory consolidation. Methods: We developed three monoclonal anti-Ng antibodies. Mass spectrometry and a novel enzyme-linked immunosorbent assay were used to analyze cerebrospinal fluid (CSF) Ng in three independent clinical cohorts including patients with AD dementia (n = 100 in total), mild cognitive impairment patients (MCI), (n = 40) and controls (n = 80 in total). Results: We show in three independent clinical cohorts a marked increase in CSF Ng levels in AD dementia (P < .001 in all studies). In addition, high CSF Ng levels at the MCI stage predicted progression to dementia due to AD with a hazard ratio of 12.8 (95% confidence interval 1.6-103.0, P = .02). In amyloid-positive MCI patients, high CSF Ng correlated with a more rapid change in cognition during clinical follow-up (P = .03). Discussion: These results suggest that CSF Ng is a novel AD biomarker that may be used to monitor synaptic degeneration, and correlates with the rate of cognitive decline in prodromal AD. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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