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Alzheimers Dement. 2016 Nov;12(11):1149-1158. doi: 10.1016/j.jalz.2016.04.005. Epub 2016 May 22.

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

Author information

1
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden. Electronic address: erika.bereczki@ki.se.
2
King's College London, Wolfson Centre for Age-Related Diseases, London, UK.
3
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
4
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden; Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry Sahlgrenska Academy, Gothenburg University, Mölndal, Sweden.
5
AstraZeneca Translational Science Centre at Karolinska Institutet, Solna, Sweden; Department of Clinical Neuroscience, Karolinska Institutet, Science for Life laboratory, Solna, Sweden.
6
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division for Neurogeriatrics, Karolinska Institutet, Stockholm, Sweden.
7
Department of Neuropathology, Institute of Pathology, University of Debrecen, Debrecen, Hungary.
8
Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK.

Abstract

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.

KEYWORDS:

Alzheimer's disease; Cognitive impairment; Dementia with Lewy bodies; Neurogranin; Parkinson's disease with dementia; Rab3A; SNAP25; Synaptic dysfunction

PMID:
27224930
DOI:
10.1016/j.jalz.2016.04.005
[Indexed for MEDLINE]

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