An immune response characterizes early Alzheimer’s disease pathology and subjective cognitive impairment in hydrocephalus biopsies

Wenrui Huang, Anne Marie Bartosch, Harrison Xiao, Suvrajit Maji, Elliot H. H. Youth, Xena Flowers, Sandra Leskinen, Zeljko Tomljanovic, Gail Iodice, Deborah Boyett, Eleonora Spinazzi, Vilas Menon, Robert A. McGovern, Guy M. McKhann and Andrew F. Teich ()
Additional contact information
Wenrui Huang: Columbia University
Anne Marie Bartosch: Columbia University
Harrison Xiao: Columbia University
Suvrajit Maji: Columbia University
Elliot H. H. Youth: Columbia University
Xena Flowers: Columbia University
Sandra Leskinen: Columbia University
Zeljko Tomljanovic: Columbia University
Gail Iodice: Columbia University
Deborah Boyett: Columbia University
Eleonora Spinazzi: Columbia University
Vilas Menon: Columbia University
Robert A. McGovern: University of Minnesota
Guy M. McKhann: Columbia University
Andrew F. Teich: Columbia University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25902-y

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