Understanding Changes in Hippocampal Interneurons Subtypes in the Pathogenesis of Alzheimer's Disease: A Systematic Review.

Background It is becoming increasingly recognized that there is significant interneuron degeneration in Alzheimer's disease (AD). As the hippocampus is integral for learning and memory, we performed a systematic review of primary literature focused on the relationship between Alzheimer's and hippocampal interneurons. Here we summarize the experimental work done to date, and identify opportunities for future experiments. OBJECTIVES This PRISMA style systematic review seeks to summarize the findings of all accessible research focussed on cholecystokinin (CCK), neuropeptide Y (NPY), parvalbumin (PV), and somatostatin (SOM) interneurons in the hippocampal formation. RESULTS 1593 papers were pulled from PubMed, PsychInfo, and Web of Science, based on three blocks of search terms. There were 45 papers that met all of the pre-determined inclusion/exclusion criteria. There is strong evidence that PV interneurons are affected early in the disease by toxic Aβ fragments, SOM interneurons indirectly while the somatostatin neuropeptide may act to slowly worsen toxic Aβ fragment accumulation, while NPY and CCK positive interneurons are affected later in the progression of the disease. CONCLUSIONS Fewer studies have been performed on NPY and CCK interneurons, and there is room for further investigations regarding the role of PV interneurons in Alzheimer's to help resolve contradictory findings. This review found that PV interneurons are affected early in the disease, but only in APP but not tau models. NPY and CCK interneurons were found to be affected later in the disease and SOM interneurons vary greatly. Future studies may consider reporting immunohistochemical studies inclusive of either cell location or morphology- as well as marker to give a more robust picture of the disease.