Alzheimer disease (AD) is the most common form of dementia and the leading cause of age-related neurodegeneration worldwide. Early symptoms include short-term memory loss and forgetfulness before progressing to mood swings, confusion and more serious memory loss. AD is pathologically characterized both by deposits of extracellular ‘plaques’ of aggregated amyloid-β protein and intracellular ‘tangles’ of hyperphosphorylated tau protein. Recent evidence suggests that there is also an important role of microglia-mediated neuroinflammation in the pathology of AD. The majority of AD cases are sporadic, although familial AD is associated with mutations in AD genes such as presenilin-1 and -2, and amyloid precursor protein (APP). Additionally, there are mutations associated with a number of genes (e.g. APOE, TREM2) that increase risk of AD, and which are predominantly expressed in microglia. There is currently no cure for AD.
In the Neuro-D group we use human post-mortem brain tissue and iPSCs differentiated into microglia to study the effects of iron accumulation in microglia and how that contributes to AD progression.