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

Erika Bereczki; Paul T. Francis; David Howlett; Joana B. Pereira; Kina Höglund; Anna Bogstedt; Angel Cedazo-Minguez; Jean-Ha Baek; Tibor Hortobágyi; Johannes Attems; Clive Ballard; Dag Aarsland

doi:10.1016/j.jalz.2016.04.005

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

Erika Bereczki, Paul T. Francis, David Howlett, Joana B. Pereira, Kina Höglund, Anna Bogstedt, Angel Cedazo-Minguez, Jean-Ha Baek, Tibor Hortobágyi, Johannes Attems, Clive Ballard, Dag Aarsland

Research output: Contribution to journal › Article › peer-review

120 Citations (Scopus)

194 Downloads (Pure)

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.

Original language	English
Pages (from-to)	1149-1158
Journal	Alzheimer's & Dementia
Volume	12
Issue number	11
Early online date	22 May 2016
DOIs	https://doi.org/10.1016/j.jalz.2016.04.005
Publication status	Published - 22 May 2016

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jalz.2016.04.005

Synaptic proteins predict cognitive decline in Alzheimer's disease_FRANCIS_Publishedonline22May2016_GREEN AAMAccepted author manuscript, 326 KB

Cite this

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title = "Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia",

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

author = "Erika Bereczki and Francis, {Paul T.} and David Howlett and Pereira, {Joana B.} and Kina H{\"o}glund and Anna Bogstedt and Angel Cedazo-Minguez and Jean-Ha Baek and Tibor Hortob{\'a}gyi and Johannes Attems and Clive Ballard and Dag Aarsland",

year = "2016",

month = may,

day = "22",

doi = "10.1016/j.jalz.2016.04.005",

language = "English",

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T1 - Synaptic proteins predict cognitive decline in Alzheimer's disease and Lewy body dementia

AU - Bereczki, Erika

AU - Francis, Paul T.

AU - Howlett, David

AU - Pereira, Joana B.

AU - Höglund, Kina

AU - Bogstedt, Anna

AU - Cedazo-Minguez, Angel

AU - Baek, Jean-Ha

AU - Hortobágyi, Tibor

AU - Attems, Johannes

AU - Ballard, Clive

AU - Aarsland, Dag

PY - 2016/5/22

Y1 - 2016/5/22

N2 - 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.

AB - 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.

KW - Dementia with Lewy bodies

KW - Alzheimer's disease

KW - Parkinson's disease with dementia

KW - Cognitive impairment

KW - Synaptic dysfunction

KW - SNAP25

KW - Rab3A

KW - Neurogranin

U2 - 10.1016/j.jalz.2016.04.005

DO - 10.1016/j.jalz.2016.04.005

M3 - Article

SN - 1552-5260

VL - 12

SP - 1149

EP - 1158

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 11

ER -