title: Meta-analysis of synaptic pathology in Alzheimer's disease reveals selective molecular vesicular machinery vulnerability.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands.
authors.forename: Martijn C
authors.initials: MC
authors.lastname: de Wilde
authors.affiliation: Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Cassia R
authors.initials: CR
authors.lastname: Overk
authors.affiliation: Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands.
authors.forename: John W
authors.initials: JW
authors.lastname: Sijben
authors.affiliation: 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: emasliah@ucsd.edu.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003933:Diagnosis; D006801:Humans; D016239:MEDLINE / Q000706:statistics & numerical data; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D033921:Vesicular Transport Proteins
keywords: Alzheimer's disease; Endosomal/lysosomal pathway; Meta-analysis; Synapse markers; Synapse number