Proteomic and non-proteomic changes of presynaptic proteins in animal models of Alzheimer's disease: A meta-analysis 2015-2023.

BackgroundSynaptic proteins are often used as markers for synaptic damage in non-clinical models of Alzheimer's disease (AD) and are known to be affected early in the disease in humans. Presynaptic protein loss has been shown to be especially strong in patients, though not all proteins and brain areas are affected equally.ObjectiveTo investigate whether presynaptic protein loss is similarly heterogenous in non-clinical AD models, a meta-analysis was conducted in rodent models of the disease.MethodsPubMed, Embase, and Medline databases were searched for publications measuring presynaptic markers in AD rodent model brains between 2015-2023. A total of 1333 records arose from the searches, and these were screened for suitable studies. Meta-analyses on global presynaptic protein changes, protein-, area- and model-specific effects amongst others were performed on 184 studies. Studies employing proteomic approaches for protein quantification were analyzed separately from non-proteomic studies.ResultsRobust and significant global loss of presynaptic proteins was observed in these animal models. The effect size varied between different model types, with the greatest effects being observed in models in which either tau was genetically modified or where amyloid-β injection was used. The greatest severity was seen in hippocampal subregions and for proteins associated with the vesicle release machinery (SNARE proteins).ConclusionsProteomic studies confirmed that presynaptic proteins were most frequently lower in AD models relative to control, although some proteins were increased. Multiple presynaptic proteins were found to be altered in proteomic meta-analysis and some of these may constitute putative biomarkers that warrant further investigation.