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Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia

Lookup NU author(s): Professor Johannes Attems, Dr Clive Ballard, Dr Dag Aarsland


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Introduction: Our objective was to compare the levels of three synaptic proteins involved in different steps of the synaptic transmission: Rab3A, SNAP25, and neurogranin, in three common forms of dementia: Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease dementia.Methods: A total of 129 postmortem human brain samples were analyzed in brain regional specific manner exploring their associations with morphologic changes and cognitive decline.Results: We have observed robust changes reflecting synaptic dysfunction in all studied dementia groups. There were significant associations between the rate of cognitive decline and decreased levels of Rab3 in DLB in the inferior parietal lobe and SNAP25 in AD in the prefrontal cortex. Of particular note, synaptic proteins significantly discriminated between dementia cases and controls with over 90% sensitivity and specificity.Discussion: Our findings suggest that the proposition that synaptic markers can predict cognitive decline in AD, should be extended to Lewy body diseases. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Publication metadata

Author(s): Bereczki E, Francis PT, Howlett D, Pereira JB, Hoglund K, Bogstedt A, Cedazo-Minguez A, Baek JH, Hortobagyi T, Attems J, Ballard C, Aarsland D

Publication type: Article

Publication status: Published

Journal: Alzheimer's & Dementia

Year: 2016

Volume: 12

Issue: 11

Pages: 1149-1158

Print publication date: 01/11/2016

Online publication date: 22/05/2016

Acceptance date: 02/04/2016

ISSN (print): 1552-5260

ISSN (electronic): 1552-5279

Publisher: Elsevier


DOI: 10.1016/j.jalz.2016.04.005


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Funder referenceFunder name
KI-Astra Zeneca
Loo och Hans Osterman foundation
Brains for Dementia research
David and Astrid Hagelens foundation
Gamla Tjanarinnor
KI Geriatric Diseases foundation
Lindhes Advokatbyra foundation
NIHR Biomedical Research Centre for Mental at King's College London
NIHR Biomedical Research Unit for Dementia at King's College London
Stohnes stiftelse
G0400074UK Medical Research Council
FP7-PEOPLE-2012-IEF-328758Marie Curie fellowship