9 research outputs found
Integrative approach to sporadic Alzheimer鈥檚 disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau
miR155 regulation of behavior, neuropathology, and cortical transcriptomics in Alzheimer's disease
The landscape of multiscale transcriptomic networks and key regulators in Parkinson鈥檚 disease
Integrative approach to sporadic Alzheimer鈥檚 disease:聽deficiency of TYROBP聽in cerebral A尾 amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing A尾 burden
Meta-Analysis of the Alzheimer's Disease Human Brain Transcriptome and Functional Dissection in Mouse Models
We present a consensus atlas of the human brain transcriptome in Alzheimer's disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington's disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies.http://deepblue.lib.umich.edu/bitstream/2027.42/177526/2/Meta-Analysis of the Alzheimers Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.pdfPublished versio