Why Removing Amyloid From the Brain Isn't Enough to Stop Alzheimer's with Dr. Jonathan Fellows | E220

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What if the gene you've been told to fear isn't actually a verdict on your future, and the disease you're racing to treat has already been silently progressing for two to three decades before anyone notices? In this episode, Dr. Jonathan Fellows joins me to challenge how we think about Alzheimer's risk, diagnosis, and treatment, making the case that early detection and lifestyle intervention matter more than the medications most people pin their hope on.

Dr. Jonathan Fellows is a neurologist with more than 25 years of clinical experience and serves as the Director of the Alzheimer's Disease and Memory Disorder Center at the Michigan Institute for Neurological Disorders, part of Corewell Health in Farmington Hills, Michigan, the largest private practice neurology group in the state.

00:00 - Introduction

00:39 - Brain Defenders: A New Way to Think About Brain Health

02:59 - Welcoming Dr. Jonathan Fellows

03:51 - Why Neurology School Doesn't Teach Prevention

05:27 - Inside the Michigan Institute for Neurological Disorders

07:44 - Starting the Conversation When a Family Gets the Alzheimer's Diagnosis

08:00 - Apraxia and the Real Warning Signs of Cognitive Decline

09:00 - Why Amyloid Alone Doesn't Equal an Alzheimer's Diagnosis

09:55 - The Centiloid Score: Measuring Amyloid in the Brain

11:21 - Blood-Based Biomarkers and the Rise of P-tau 217

13:19 - Elevated P-tau 217 at 40: A Wake-Up Call You Can't Ignore

13:32 - Habits in Your 30s and 40s vs. Disease in Your 60s and 70s

16:53 - 40 Hz Light Therapy and Cognitive Decline

18:53 - Why Not Every Amyloid-Positive Patient Should Get Anti-Amyloid Drugs

21:00 - Alzheimer's Drug Therapy Today vs. Where MS Treatment Stood in the 90s

23:59 - Why Early and Presymptomatic Detection Matters

25:21 - Will Anti-Amyloid Drugs Be Pushed to Presymptomatic Patients?

25:39 - What We Know for a Fact About Lifestyle and Disease Progression

26:27 - A Real Patient Case: When to Say No to Anti-Amyloid Drugs

28:30 - APOE Explained: The Gene That Changes Your Alzheimer's Risk

31:49 - 3X4 Genetics: Your DNA Isn't a Verdict

33:47 - How Exercise Can Offset APOE4 Risk

34:10 - APOE4 Is Not Deterministic — and Saying Otherwise Is Malpractice

34:51 - Down Syndrome, Presenilin, and the Truly Deterministic Cases

35:42 - ARIA Risk and Why Europe Restricts Anti-Amyloid Drugs for APOE4 Carriers

38:00 - Where Anti-Amyloid Drugs Still Fit in Treatment

39:14 - Current Clinical Trials at the Michigan Institute

39:49 - Programmable Microglia: The Brain's Immune System Explained

41:01 - Good Twin, Bad Twin: How Microglia Switch From Protector to Threat

42:09 - Beta-Amyloid as an Antimicrobial Defender? Rethinking the Enemy Narrative

42:49 - Insulin Resistance and the Brain-Metabolism Connection

43:41 - The Diabetes Epidemic Hiding in Plain Sight

43:58 - The Rainbow Lunchbox: A Preschooler Who Got It Wrong and Right

44:49 - Why a Third of Americans Are Pre-Diabetic and Don't Know It

46:30 - Closing Thoughts

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