Data related to "Tau, amyloid-beta and alpha-synuclein co-pathologies synergistically enhance neuroinflammation and neuropathology"
Publication Date
8-22-2025
Abstract
Manuscript Abstract
Alzheimer’s and Parkinson disease pathology can co-occur, with amyloid-beta and phosphorylated tau, found in over half of Parkinson disease cases. Alpha-synuclein inclusions, a hallmark of Parkinson disease, are present in over 30% of Alzheimer’s cases and the co-expression of these pathologies is linked to faster cognitive decline and earlier death. Immune activation is a hallmark of both diseases, but current model systems primarily examine each pathology in isolation. As such, how these co-pathologies interact to drive inflammation and neuronal loss remain poorly understood. To address this, we developed a co-pathology mouse model combining tau, amyloid-beta, and alpha-synuclein. Here, we show that co-pathologies synergistically trigger a distinct and amplified neuroimmune response, marked by robust expansion of CD4+ and CD8+ tissue-resident memory T cells and increased CD68+ microglia, a population of activated, phagocytosing microglia, compared to single pathology brains. These changes were abundant in the hippocampus and cortex, regions showing elevated Aβ protein pathology load and enhanced neuronal loss with co-pathology expression. Our findings demonstrate that co-pathologies act synergistically to enhance immune activation prior to neurodegeneration. This model provides a platform for assessing mixed-pathology mechanisms and identifies key immune cell populations that may drive disease acceleration across Alzheimer’s, Parkinson disease and their related dementias.
Repository
Zenodo
Distribution License
This work is licensed under a Creative Commons Attribution 4.0 International License.
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