Dr. Dale Bredesen

Dr. Bredesen graduated from Caltech and received his MD from Duke.  He trained with Nobel laureate Prof. Stanley Prusiner, and was the Founding President of the Buck Institute for Research on Aging. His research led to over 230 published papers, and the first reversal of cognitive decline in patients with Alzheimer’s disease, using a precision medicine protocol. He is the author of two New York Times best sellers, and is Senior Director of the world’s first precision medicine program for neurodegenerative diseases, at the Pacific Neuroscience Institute.

00:00 – 01:48 | Introduction

• Dr. Barrett introduces a rebroadcast of his conversation with renowned neurologist Dr. Dale Bredesen
• Discussion of Bredesen’s seminal book “The End of Alzheimer’s” (circa 2017)

• Context on why this episode is important given the prevalence of cognitive decline

01:48 – 03:51 | Dr. Bredesen’s Background

• Training at prestigious institutions: Caltech, MIT, Duke (medical school and internal medicine), UCSF (neurology)
• Worked with two Nobel laureates
• Ran a research laboratory for 30 years
• Focus on neurodegenerative disease – historically the area of greatest biomedical therapeutic failure
• Unique position combining bench science with clinical practice (translational medicine)

03:51 – 06:14 | Breakthrough in Disease Modeling

• 1994: Developed ability to model neurodegenerative diseases in cell culture
• Used mutations associated with Alzheimer’s and ALS to study disease mechanisms
• Key finding: Cells with disease-causing mutations became hypersensitive to cell death
• Created first systems to study neurodegeneration in a dish

06:14 – 13:58 | Amyloid Precursor Protein (APP) – The Molecular Switch

• Evolution selects for performance over durability (antagonistic pleiotropy)
• Nervous system has tremendous capabilities but Achilles heels for durability
• APP functions as a molecular switch with two modes:
  • Connection mode: When conditions are good, APP is cleaved at alpha site → produces peptides that signal growth and memory formation
  • Protection mode: Under stress/insult, APP is cleaved at three sites → produces four peptides including amyloid beta
• Amyloid beta is actually an antimicrobial peptide responding to insults
• Brain shifts resources from connection to protection (like pandemic shutdown analogy)
• ApoE4 genetic variant promotes inflammatory/protective state
• System involves positive feedback loops (like blood clotting, not homeostatic)

13:58 – 17:46 | Understanding the Disease Mechanism

• Amyloid beta feeds back to prevent alpha cleavage, maintaining protection mode
• Prionic loops amplify the protective response
• System designed to fight insults until they’re cleared, then reset
• Explains why simply removing amyloid doesn’t cure the disease

17:46 – 23:32 | ApoE Genetics and Risk

• ApoE4 interacts with 1,700 genes, promoting pro-inflammatory state
• ApoE4 enters nucleus and alters gene transcription
• Risk levels by genotype:
  • ApoE 3/3: 9% lifetime risk
  • One ApoE4 copy: 30% lifetime risk
  • Two ApoE4 copies: 90% lifetime risk (recent research)
• ApoE4 was advantageous in environments with more infectious threats
• Example: Julie G (ApoE 4/4) had symptoms in late 40s, now thriving in early 60s on protocol

23:32 – 29:12 | Development of Treatment Protocol

• Initial drug screening identified compounds that shift from protection to connection mode
• Example: Tropisetron (anti-emetic used in 39 countries)
• 2011 breakthrough: Realized single drug approach was insufficient
• Paradigm shift: Address the entire network causing the protective response
• Must remove insults rather than just suppress amyloid
• Criticism of current amyloid-removal therapies as “barbaric” – like removing a patch from a tire
• Requires personalized approach identifying specific pathogens and toxins

29:12 – 32:46 | Research Funding and Medical Paradigm

• $3.7 billion spent by NIH in 2023 on Alzheimer’s research
• None directed toward Bredesen’s approach
• Historical parallel to scurvy: took centuries for medical establishment to accept solution
• Comparison to FINGER trial from Finland (limited to 4 interventions, not personalized)
• Currently conducting randomized controlled trial at six sites
• Standard medical review processes create impediments to paradigm shifts

32:46 – 36:47 | Influence of Functional Medicine

• Dr. Bredesen’s wife is a functional medicine doctor
• Initial skepticism about functional medicine approach
• Realization that molecular pathways aligned perfectly with functional medicine principles
• Hundreds of interventions available (exercise, nutrition, sleep, inflammation control, etc.)
• Integration of lab findings with functional medicine created comprehensive treatment arsenal
• Examples: ashwagandha, Rhodiola, whole coffee fruit extract for BDNF
• Importance of checking for sleep apnea, oral microbiome changes, chronic infections

36:47 – 40:03 | Comprehensive Patient Evaluation

• Need thorough history and appropriate testing
• Must check for chronic infections not typically evaluated
• Oxygen saturation issues (sleep apnea, UARS)
• Fight-or-flight mode and limbic system hypersensitivity
• Case example: Patient with posterior cortical atrophy improved after treating Bartonella and mycotoxin exposure
• These evaluations are “critical” but not part of standard Alzheimer’s care

40:03 – 43:21 | Pushback from Establishment

• Alzheimer’s Association does not recognize the program
• Heavily influenced by pharmaceutical industry
• Successful clinical trial results published two years ago
• Schism between “prescription pad medicine” and “21st century precision medicine”
• Similar developments in autism treatment

43:21 – 45:17 | Rising Incidence and Environmental Factors

• Autism and early-onset Alzheimer’s both skyrocketing
• Greatest increases in Alzheimer’s are in 30s, 40s, and 50s age groups
• Disease starts biochemically 20 years before diagnosis
• Contributing factors:
  • Ultra-processed foods (ubiquitous since 1960s-70s)
  • Insulin and leptin resistance
  • Increased toxin exposure
  • Mycotoxin-laden homes
  • High fructose corn syrup and engineered foods
  • 80 million Americans have metabolic syndrome

45:17 – 48:48 | Diabetes Medications Discussion

• SGLT-2 inhibitors discussed as potential intervention
• Semaglutide concerns: muscle mass loss, gut microbiome effects, cost
• SGLT-2 may help by urinating out glucose
• Main concern: infections (especially UTIs in females)
• Could be useful as temporary “biohack” for motivated patients

48:48 – 53:03 | Long-term Treatment Approach

• Importance of weaning off medications when possible
• Example: Aricept (cholinesterase inhibitor) – studies show worse outcomes after 2-5 years
• New paper showing sustained improvement over a decade (unprecedented in Alzheimer’s)
• Success due to improving underlying physiology
• Seven basic principles:
  1. Diet
  2. Exercise
  3. Sleep
  4. Stress management
  5. Brain training
  6. Detox
  7. Targeted supplements
• Plus precision interventions for specific infections/toxins
• New program: “Get a Brain Scan” – available in 47 states for p-tau 217 and GFAP testing
• Early detection analogy to pre-diabetes screening

53:03 – 58:23 | Training and Replication

• Over 2,000 physicians trained in 10 countries
• Dr. Heather Sanderson’s independent trial replicated results (published in “Reversing Alzheimer’s”)
• Compassionate use justification for early availability
• Historical parallel to childhood leukemia treatment (Dr. Dana Farber, 1960s)
• Patient Zero (treated 2012) now 80 years old, working as brain health coach and yoga instructor

58:23 – End | Final Recommendations

• Everyone should know their ApoE status
• Mainstream medicine has approach “backward” – waiting until disease progresses
• Key recommendation: Cognoscopy for everyone 40+
  • Simple blood tests
  • Online cognitive test
  • MRI with volumetrics only if symptoms present
  • Available at mycognoscopy.com
• “Alzheimer’s is rapidly becoming optional”

Closing

• Sponsor messages about nitric oxide supplementation and other products
• Standard podcast disclaimers

Key Takeaway: Dr. Bredesen presents Alzheimer’s as a protective response to multiple insults (infections, toxins, metabolic dysfunction) rather than a single-cause disease, requiring personalized, multi-modal intervention addressing root causes rather than just suppressing symptoms.

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