Tau, amyloid-β and α-synuclein co-pathologies synergistically enhance neuroinflammation and neuropathology.

ABSTRACT: Alzheimer's (AD) and Parkinson disease (PD) pathology often co-occur. Amyloid-β and phosphorylated tau are found in 30-50% of idiopathic PD cases, while α-synuclein inclusions are present in 50% of AD cases. These co-pathologies are linked to increased mortality and earlier onset of cognitive decline. Immune activation is a hallmark of these neurodegenerative diseases, but current models primarily examine each pathology in isolation. How these co-pathologies drive inflammation and neuronal loss remains poorly understood. We therefore developed a mouse model combining tau, amyloid-β, and α-synuclein. We found that co-pathologies synergistically trigger an amplified neuroimmune response, with expanded populations of CD4⁺ and CD8⁺ tissue-resident memory T cells and CD68<

SUBMITTER: Webster JM 

PROVIDER: S-EPMC12424655 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature