Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration

AD and PD are the most common neurodegenerative diseases and affect millions of people worldwide. Currently the molecular mechanism of disease pathogenesis remains unclear and there are no therapies can prevent, slow, or halt disease progression.

The commonalities and differences in cell-type-specific pathways that lead to Alzheimer disease (AD) and Parkinson disease (PD) remain unknown. Here, we performed a single-nucleus transcriptome comparison of control, AD and PD striata. We describe three astrocyte subpopulations shared across different brain regions and evolutionarily conserved between humans and mice. We reveal common features between AD and PD astrocytes and regional differences that contribute toward amyloid pathology and neuro degeneration. In contrast, we found that transcriptomic changes in microglia are largely unique to each disorder. Our anal ysis identified a population of activated microglia that shared molecular signatures with murine disease-associated microglia (DAM) as well as disease-associated and regional differences in microglia transcriptomic changes linking microglia to disease-specific amyloid pathology, tauopathy and neuronal death. Finally, we delineate undescribed subpopulations of medium spiny neurons (MSNs) in the striatum and provide neuronal transcriptomic profiles suggesting disease-specific changes and selective neuronal vulnerability. Below is the link to the full story.

1. Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration
   Jinbin Xu*, Huifangjie L. Farsad, Yiran Hou, Kia Barclay, Ben Anthony Lopez, Shinnosuke Yamada, Ibrahim Olabayode Saliu, Yiming Shi, William C. Knight, Randall J. Bateman, Tammie L. S. Benzinger, Jason J. Yi, Qingyun Li, Ting Wang, Joel S. Perlmutter, John C. Morris & Guoyan Zhao* (*co-corresponding), Nature Aging (2023).