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

Alzheimers Dement. 2016 Jun;12(6):633-44. doi: 10.1016/j.jalz.2015.12.005. Epub 2016 Jan 14.


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.

Keywords: Alzheimer's disease; Endosomal/lysosomal pathway; Meta-analysis; Synapse markers; Synapse number.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / pathology*
  • Brain / pathology*
  • Clinical Trials as Topic / statistics & numerical data
  • Diagnosis
  • Humans
  • MEDLINE / statistics & numerical data
  • Synapses / metabolism*
  • Synapses / pathology
  • Vesicular Transport Proteins / metabolism*


  • Vesicular Transport Proteins