Meta-analysis of synaptic pathology in Alzheimer's disease reveals selective molecular vesicular machinery vulnerability.

Martijn C de Wilde, Cassia R Overk, John W Sijben, Eliezer Masliah

Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association 2017;12(6):633-44

PMID: 26776762

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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.

Address: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands.; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA; Department of Pathology, University of California, San Diego, La Jolla, CA, USA. Electronic address: [email protected].

DOI: 10.1016/j.jalz.2015.12.005