Association of Amyloid-ß, Tau and α-Synuclein pathology with microglia subregional responses in the hippocampus 

In Alzheimer’s Disease (AD) and Dementia with Lewy Bodies (DLB) the brain areas linked to memory processes are particularly affected. However, hippocampal atrophy follows a differential subregional pattern, with an exacerbated volume loss in CA1 of AD patients. We hypothesized that the distribution and severity of AD- and DLB-related proteinopathies (PP), as well as the alteration of microglia, the brain innate immune cells, could exacerbate the local deterioration of the hippocampus in AD.

To quantify Amyloid-ß (Aß), P-Tau and P-Synuclein (P-Syn) loads and associated microglia morphology, we used high-content confocal microscopy and AI-assisted 3D image analysis applied on post-mortem hippocampi from patients with neurodegenerative changes and age-matched controls.

Across AD and DLB samples, we found that the subregional load patterns were PP-dependent. The highest loads for all three PP were found in AD, with P-Tau and P-Syn pathologies exacerbated in CA1. Our morphological analysis of 35000 individual microg

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