Toxins Rewrite Your Genes (And Trigger Brain Disease) with Dr. Sarah Marzi E209

🧠 Stay ahead with the latest in science, nutrition, and wellness by subscribing to Dr. Perlmutter’s newsletter at: ✉️🌱 Thank you to our sponsors: EVY - and the code perlmutter26 will be auto-applied to your order to get $200 off & free shipping (90 days risk-free). Fresh Pressed Olive Oil - For a complimentary bottle of one of the greatest olive oils I've ever discovered. 3x4 Genetics - for a special offer when you sign up to decode your genetics and get personalized, science-backed health recommendations. ==== Dr. Perlmutter’s groundbreaking new book, Brain Defenders, is now available for pre-order. Discover how to protect your brain and future health - reserve your copy today at ==== On this episode of The Empowering Neurologist, I’m joined by Dr. Sarah Marzi, a neuroscientist at King’s College London and a principal investigator at the UK Dementia Research Institute, whose work is transforming how we understand neurodegenerative disease risk. Dr. Marzi’s research focuses on gene regulation in the human brain, particularly within microglia, the immune cells that orchestrate inflammation, synaptic pruning, and repair. Her studies show that genetic risk for diseases like Alzheimer’s is concentrated not in protein-coding genes, but in regulatory regions of the genome, epigenetic switches that control immune behavior in the brain. This conversation with Dr. Marzi is not just about disease. It’s about agency. Understanding epigenetics helps explain how lifestyle, environment, and immune balance can influence brain destiny. It’s science that empowers prevention, resilience, and hope. ==== 00:00 Intro 03:12 Epigenetics and Neurodegenerative Disease 04:49 Why Alzheimer’s Is Not a Single Gene Disorder 09:18 Protein Aggregation and Brain Cleanup Failure 10:55 Microglia vs Neurons in Alzheimer’s 19:04 Blood Brain Barrier and Inflammatory Signaling 20:39 ApoE Genetics Explained 23:37 Human Microglia Transplanted Into Mouse Brain 30:02 Vitamin D Receptor and Protective Gene Programs 38:18 Environmental Toxins and Parkinson’s 44:59 C1q Activation and Synapse Loss 49:33 Why Substantia Nigra Is Uniquely Vulnerable 51:39 Paraquat, Mitochondria and Converging Toxic Pathways 53:00 Epigenetic Memory of Toxic Exposure 54:09 Histones and Gene Regulation in Alzheimer’s 57:41 Oligodendrocytes as a Hidden Player 59:32 Why Single Target Drugs May Fail 01:02:10 Detecting Disease Through Blood and Machine Learning 01:04:41 Can Lifestyle Modify Epigenetics ==== Dr Sarah Marzi is a Senior Lecturer in Neuroscience at King’s College London and a Group Leader at the UK Dementia Research Institute. Her work focuses on how our genes and environment change cellular processes in the brain and can predispose us to neurodegenerative diseases such as Alzheimer’s, Parkinson’s and motor neuron disease. An expert in epigenetics – the chemical switches that turn genes on and off – Dr Marzi uses cuttingedge genomic techniques on human brain tissue as well as cell and animal models. Her team combines these experiments with advanced statistics, bioinformatics and AI to map the earliest molecular changes that make brain cells vulnerable to disease, particularly in immune cells of the brain called microglia. This work aims to reveal how both genetic variants and environmental exposures, including pesticides, contribute to disease risk and to uncover new avenues for therapy. ___________________________ Instagram: Website:

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Toxins Rewrite Your Genes (And Trigger Brain Disease) with Dr. Sarah Marzi E209 is an episode from The Empowering Neurologist Podcast by David Perlmutter.

This episode is 01:12:57 long.

This episode was published on Feb 17, 2026.

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