The Role of PICALM in Regulating Neurogenesis in Alzheimer's Disease

Summary

This research project investigates the role of the PICALM gene in regulating adult hippocampal neurogenesis (AHN) and beta-amyloid precursor protein (b-APP) metabolism, aiming to understand how its altered expression contributes to Alzheimer's disease pathology and memory deficits.

What they want

The project hypothesizes that PICALM regulates AHN and b-APP metabolism, and that altered PICALM expression in neural stem and progenitor cells (NSPCs) in late-onset Alzheimer's disease (LOAD) impairs AHN, leading to amyloidosis and hippocampus-dependent memory deficits. Aim 1 will use conditional knockout of PICALM in mice to examine its role in AHN and AHN-dependent learning and memory. Aim 2 will elucidate PICALM's role in impaired neurogenesis and amyloidosis in Alzheimer's disease using human induced pluripotent stem cell (iPSC)-derived forebrain neurons with PICALM polymorphisms and PICALM knockout.

Deliverables

New information about a novel regulator of hippocampal neurogenesis
Mechanism by which AHN is impaired in LOAD
Understanding of PICALM's contribution to AD pathology and memory loss

Technical requirements

Conditional knockout of PICALM in mice
iPSC-derived human forebrain neurons
PICALM knockout in iPSC-derived cells
Analysis of b-III-tubulin and neurofilament levels
Analysis of b-APP metabolism
Assessment of AHN-dependent learning and memory