EMBO Mol Med. 2016 Sep 1;8(9):1005-18. doi: 10.15252/emmm.201606520. Print 2016 Sep.
miR-132 loss de-represses ITPKB and aggravates amyloid and TAU pathology in Alzheimer's brain.
Salta E 1, Sierksma A 1, Vanden Eynden E 1, De Strooper B 2.
microRNA-132 (miR-132) is involved in prosurvival, anti-inflammatory and memory-promoting functions in the nervous system and has been found consistently downregulated in Alzheimer's disease (AD). Whether and how miR-132 deficiency impacts AD pathology remains, however, unaddressed. We show here that miR-132 loss exacerbates both amyloid and TAU pathology via inositol 1,4,5-trisphosphate 3-kinase B (ITPKB) upregulation in an AD mouse model. This leads to increased ERK1/2 and BACE1 activity and elevated TAU phosphorylation. We confirm downregulation of miR-132 and upregulation of ITPKB in three distinct human AD patient cohorts, indicating the pathological relevance of this pathway in AD.