Alzheimer’s Disease, Piezo2 Channelopathy, Piezo1 Channelopathy and the Body-Wide Piezo2 System

A PIEZO2 variant was shown recently to protect against Alzheimer’s disease in the Hispanic population. This analysis implicates the potentially critical role of Piezo2 in Alzheimer’s disease pathophysiology. Another recent research mimicked acquired Piezo1 channelopathy by PIEZO1 manipulation. This study also showed that phosphatidylinositol 4,5-bisphosphate (PIP2) administration ameliorated brain capillary endothelial Piezo1 channelopathy in a mouse model of Alzheimer’s disease. However, the initiating microdamage is suggested to be in the prefrontal cortex further upstream of pathophysiology, namely an irreversible Piezo2 channelopathy of glutamatergic terminals that should fine modulate oxytocin release along stressful ultradian events. Implication of Piezo2 in the defensive arousal response reveals an underlying body-wide Piezo2 system of which the proposed prefrontal Piezo2 channelopathy posits a critical locus. PIP2 is emerging as a potential treatment method of Piezo channelopathy in Alzheimer’s disease, however the challenge remains how it could be administered more precisely to affected brain areas.