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

Alzheimer's & Dementia - Tập 12 - Trang 633 - 2016
Martijn C. de Wilde1, John W. Sijben1, Eliezer Masliah2,3, Cassia R. Overk4
1Nutricia Advanced Medical Nutrition, Nutricia Research, Utrecht, The Netherlands
2Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
3Department of Pathology; University of California San Diego; La Jolla, CA USA.
4Department of Neurosciences, University of California–San Diego, La Jolla, CA, USA;

Tóm tắt

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.

Từ khóa

#Alzheimer's disease #Endosomal/lysosomal pathway #Meta-analysis #Synapse markers #Synapse number

Tài liệu tham khảo

null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null null