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

被引：126

作者：

Bereczki, Erika ^{[1
]}

Francis, Paul T. ^{[2
]}

Howlett, David ^{[2
]}

Pereira, Joana B. ^{[3
]}

Hoglund, Kina ^{[1
,4
]}

Bogstedt, Anna ^{[5
,6
]}

Cedazo-Minguez, Angel ^{[1
]}

Baek, Jean-Ha ^{[1
]}

Hortobagyi, Tibor ^{[7
]}

Attems, Johannes ^{[8
]}

Ballard, Clive ^{[2
]}

Aarsland, Dag ^{[1
]}

机构：

[1] Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Stockholm, Sweden

[2] Kings Coll London, Wolfson Ctr Age Related Dis, London WC2R 2LS, England

[3] Karolinska Inst, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Stockholm, Sweden

[4] Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden

[5] Karolinska Inst, AstraZeneca Translat Sci Ctr, Solna, Sweden

[6] Karolinska Inst, Dept Clin Neurosci, Sci Life Lab, Solna, Sweden

[7] Univ Debrecen, Inst Pathol, Dept Neuropathol, Debrecen, Hungary

[8] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England

来源：

ALZHEIMERS & DEMENTIA | 2016年 / 12卷 / 11期

基金：

英国医学研究理事会;

关键词：

Dementia with Lewy bodies; Alzheimer's disease; Parkinson's disease with dementia; Cognitive impairment; Synaptic dysfunction; SNAP25; Rab3A; Neurogranin; PARKINSONS-DISEASE; VISUAL-CORTEX; AMYLOID-BETA; BODIES; PATHOLOGY; TAU; IMPAIRMENT; NEURODEGENERATION; ASSOCIATION; NEUROGRANIN;

D O I：

10.1016/j.jalz.2016.04.005

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：1149 / 1158

页数：10

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