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

Alzheimer's & Dementia : the Journal of the Alzheimer's Association
Martijn C de WildeEliezer Masliah

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.

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Citations

Apr 5, 2017·Journal of Alzheimer's Disease : JAD·Karim BennysUNKNOWN MAPT-DSA Study group
Jan 29, 2017·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Cassia Overk, Eliezer Masliah
Jan 7, 2017·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·UNKNOWN Alzheimer's Association Calcium Hypothesis Workgroup
Aug 31, 2019·European Journal of Nuclear Medicine and Molecular Imaging·Christine BastinEric Salmon
Nov 9, 2019·Molecular & Cellular Proteomics : MCP·Hazal HayturalSusanne Frykman
Feb 6, 2020·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Siegfried KasperMaría Sagrario Manzano Palomo
May 14, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Adam P MeccaChristopher H van Dyck
Jul 16, 2020·The Journal of Pharmacy and Pharmacology·Fanxing XuZhenzhong Wang
Dec 24, 2017·Acta Neuropathologica·Christopher M HenstridgeTara L Spires-Jones
Aug 26, 2020·Alzheimer's Research & Therapy·Amira Latif-HernandezDetlef Balschun
May 15, 2018·Frontiers in Aging Neuroscience·Paula Garcia-EsparciaIsidro Ferrer
Mar 4, 2020·Alzheimer's Research & Therapy·Martí Colom-CadenaUNKNOWN Synaptic Health Endpoints Working Group
Sep 12, 2020·Biomarker Insights·Elena CamporesiHenrik Zetterberg
Jun 28, 2017·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Nick van WijkCharlotte E Teunissen
Oct 27, 2017·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Martijn C de WildeJohn W Sijben
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Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Hazal HayturalSusanne Frykman
Jan 8, 2021·Frontiers in Cellular Neuroscience·Jaichandar SubramanianMarie-Ève Tremblay
Mar 25, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ming-Kai ChenRichard E Carson
Apr 17, 2021·Alzheimer's & Dementia : Translational Research & Clinical Interventions·Xiaoyan SunBin Zhang
May 20, 2020·Progress in Neurobiology·Gael Barthet, Christophe Mulle
May 25, 2021·Frontiers in Aging Neuroscience·Weiqi BaoYiyun Henry Huang
Jun 8, 2021·NeuroImage. Clinical·Giordano CecchettiMassimo Filippi
Jun 29, 2021·Frontiers in Molecular Neuroscience·Svetlana TutukovaLuis R Hernandez-Miranda

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