SHANK3 and Alzheimer disease: In the hippocampal CA1 region of sporadic AD cases, miR-146a and miR-34a were both significantly upregulated and have been shown to downregulate a number of target mRNAs involved in immune and synaptic regulation, including CFH, SHANK3, and TREM2, further implicating miRNA dysregulation in both complement activation and synaptic vulnerability in AD [354].