Early Alzheimer’s disease (AD) pathology can be found in cortical biopsies taken during shunt placement for Normal Pressure Hydrocephalus. This represents an opportunity to study early AD pathology in living patients. Here we report RNA-seq data on 106 cortical biopsies from this patient population. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of biopsy β-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Taken together, these findings highlight a restricted set of microglial and non-microglial genes that correlate with early AD pathology in the setting of subjective cognitive decline.
Bibliographical noteFunding Information:
This work was supported by NIH grants K08-AG049938 (to A.F.T.) and K76-AG054868 (to A.F.T.) and with support from the Thompson Family Foundation. We would also like to acknowledge Richard Hickman for assistance with developing the tau grading system.
© 2021, The Author(s).
- Age of Onset
- Aged, 80 and over
- Alzheimer Disease/complications
- Cerebral Cortex/cytology
- Cognitive Dysfunction/diagnosis
- Gene Regulatory Networks/immunology
- Hydrocephalus, Normal Pressure/genetics
- Neuropsychological Tests
- Retrospective Studies
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural