An immune response characterizes early Alzheimer’s disease pathology and subjective cognitive impairment in hydrocephalus biopsies
| Autor: | Deborah Boyett, Elliot H H Youth, Vilas Menon, Xena E. Flowers, Suvrajit Maji, Anne Marie W. Bartosch, Sandra Leskinen, Harrison Xiao, Robert A. McGovern, Guy M. McKhann, Gail Iodice, Andrew F. Teich, Eleonora F Spinazzi, Zeljko Tomljanovic, Wenrui Huang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Pathology medicine.medical_specialty Biopsy Science General Physics and Astronomy Disease Neuropsychological Tests General Biochemistry Genetics and Molecular Biology Article Immune system Normal pressure hydrocephalus Alzheimer Disease medicine Humans Cognitive Dysfunction Gene Regulatory Networks RNA-Seq Cognitive decline Age of Onset Neurodegeneration skin and connective tissue diseases Aged Retrospective Studies Aged 80 and over Cerebral Cortex Multidisciplinary medicine.diagnostic_test business.industry General Chemistry Alzheimer's disease medicine.disease Phenotype Hydrocephalus Normal Pressure Hydrocephalus Computational biology and bioinformatics Astrocytes Female Microglia sense organs business |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Specific transcriptional changes in microglia associated with Alzheimer’s disease have been reported. Here, the authors show that transcriptional analysis of human hydrocephalus biopsies identifies changes in immune response genes associated with early AD pathology, including cognitive decline. |
| Databáze: | OpenAIRE |
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