This week on The Genetics Podcast, Patrick is joined by Dr. Sarah Marzi, Senior Lecturer at King's College London and group leader at the UK Dementia Research Institute. They discuss the impact of genes and environment on neurodegenerative disease, including: how APOE genotype shapes microglial function, how cell type-specific epigenomics of postmortem brain tissue is revealing the role of microglia and oligodendrocytes in Alzheimer's disease, and how pesticide exposure drives selective dopaminergic neuron loss and neuroinflammation in Parkinson's.
Show Notes
0:00 Intro to The Genetics Podcast
00:59 Welcome to Sarah
02:13 Environmental contributions to Parkinson’s disease and ALS
05:01 The role of microglia in Alzheimer’s disease and findings from a study on APOE variants in a mouse model
12:50 APOE4 effects on lipid accumulation, microglial activation, and vitamin D receptor signaling
14:20 Building a multi-omic atlas of the Alzheimer’s brain
18:01 Overview of the pathological cascade of events in the Alzheimer’s brain
20:31 Anti-amyloid therapies, early intervention, and combination treatment strategies
22:24 Rotenone exposure and microglial immune activation in Parkinson’s disease
29:24 Dopaminergic neuron vulnerability to pesticide exposure and mitochondrial dysfunction
31:04 Familial Parkinson’s genes, polygenic Alzheimer’s risk, and genetically targeted clinical trials
33:13 Polygenic risk and microglial cell state regulation in Alzheimer’s disease
34:13 Defining cell states in single cell RNA sequencing
35:30 Oligodendrocyte epigenetic and transcriptional changes in Alzheimer’s disease
37:23 Sarah’s most memorable hiking adventures
38:58 Closing remarks
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