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Abstract Details

Single-Cell Transcriptomics of the Microglial Complement Pathway in the Progression of Alzheimer’s Dementia
Aging, Dementia, and Behavioral Neurology
Aging and Dementia Posters (7:00 AM-5:00 PM)
002
To investigate the change in the expression level of genes related to complement pathway in human microglia. 
Inappropriate activation of complement-related pathway and microglia are known to mediate early synaptic loss in Alzheimer’s disease (AD). However, at a single microglial cell level, data on the change in the expression level of genes associated with complement-related pathway are scarce. 
We analyzed raw RNA sequencing data obtained from the ROSMAP (Religious Orders Study and Memory and Aging Project) cohorts (Frigerio et al., 2019). The quantification of transcript expression levels and differential expression were performed using the Cell Ranger and Seurat R package, respectively. Transcript expression levels are shown with average log2 fold changes (l2FC) and adjusted P values. 
We obtained 21,511 microglial cells from 12 participants, consisting of 5 patients with mild cognitive impairment (MCI), 5 with AD, and 1 normal control. The expression of C1QA and C1QB were significantly increased in AD patients compared to the control (C1QA, l2FC 0.458, P value 6e-81; C1QB, l2FC 0.321, P value 4e-52). C1QA expression was increased also in early phase of disease progression (MCI vs control: C1QA, l2FC 0.324, adjusted P value 1e-54). 
The expression levels of subcomponent of C1Q, the initiating protein of the classical complement cascade, were increased over the progression of AD. 
Authors/Disclosures
Takahisa Mikami, MD (Massachusetts General Hospital)
PRESENTER 		Dr. Mikami has nothing to disclose.
Michael Levy, MD, PhD, FÂ鶹´«Ã½Ó³»­ (Massachusetts General Hospital/Harvard Medical School) Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.