Meta-analysis of Synaptic Pathology in Alzheimer's Disease Reveals Selective Molecular Vesicular Machinery Vulnerability

Overview

Journal Alzheimers Dement

Specialties Neurology
Psychiatry

Date 2016 Jan 19

PMID 26776762

Citations 129

Authors

Martijn C de Wilde

Cassia R Overk

John W Sijben

Eliezer Masliah

Affiliations

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Abstract

Introduction: Loss of synapses best correlates to cognitive deficits in Alzheimer's disease (AD) in which oligomeric neurotoxic species of amyloid-β appears to contribute synaptic pathology. Although a number of clinical pathologic studies have been performed with limited sample size, there are no systematic studies encompassing large samples. Therefore, we performed a meta-analysis study.

Methods: We identified 417 publications reporting postmortem synapse and synaptic marker loss from AD patients. Two meta-analyses were performed using a single database of subselected publications and calculating the standard mean differences.

Results: Meta-analysis confirmed synaptic loss in selected brain regions is an early event in AD pathogenesis. The second meta-analysis of 57 synaptic markers revealed that presynaptic makers were affected more than postsynaptic markers.

Discussion: The present meta-analysis study showed a consistent synaptic loss across brain regions and that molecular machinery including endosomal pathways, vesicular assembly mechanisms, glutamate receptors, and axonal transport are often affected.

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