The role of capillary pericytes and LRP-1 in Parkinson's disease and dementia

I previously showed that in Alzheimer's disease (AD) amyloid beta constricts brain capillaries via signalling to pericytes.

I now wish to investigate: (1) Parkinson's disease (PD) / Lewy Body Dementia (DLB), where alpha-synuclein evokes ROS production and hypothesise that endothelin will be released (as observed in AD) and evoke pericyte-mediated capillary constriction to decrease cerebral blood flow. (2) The role of APOE receptor LRP-1 in regulating increased tau phosphorylation in AD.

LRP-1 is a master regulator of tau uptake/spread and highly expressed on pericytes. In AD model mice, pericyte deficiency leads to tau pathology and early neuronal loss. Thus, pericyte LRP-1 may play an important role in clearing/processing tau in the setting of amyloid pathology.

I will examine whether AD-like tau pathology develops in an APP knock-in AD/pericyte-LRP-1 deficient mouse model. (3) The effect of Covid-19 on live human pericytes and capillaries.