Wide release: April 24, 2026. Not medical advice.
Nick Jikomes talks to Dr. Andrew Pieper about how Alzheimer’s has long been viewed as irreversible but recent work shows that recovery is possible in mouse models when mitochondrial function is restored. They cover the limits of classic theories of Alzheimer’s Disease, the role of mitochondrial function and NAD balance, and a neuroprotective compound (P7C3) that enhances neuronal survival under stress.
TOPICS DISCUSSED:
Classic Alzheimer’s pathology: amyloid plaques and tau tangles identified over 120 years ago, long assumed to drive irreversible neuron loss.
Limitations of amyloid focus: plaques appear in some cognitively normal brains; antibody therapies have shown limited clinical benefit.
Metabolic perspective: brain energy failure as a tipping point where repair mechanisms are overwhelmed, linking genetics, injury, and aging.
Neuroprotection via P7C3 compounds: discovered through hippocampal neurogenesis screen; preserves mitochondrial function and normalizes NAD/NADH ratio without elevating NAD excessively.
Recovery in models: treatment after symptom onset reversed cognitive deficits, blood-brain barrier damage, oxidative stress, and axon issues in amyloid and tau mouse models, despite persistent plaques.
Broader implications: energy restoration enables surviving neurons to function; similar protective effects seen in TBI and other organs under stress.
ABOUT THE GUEST: Andrew Pieper, MD, PhD, is a board-certified psychiatrist and neuroscientist, professor at Case Western Reserve University, and director of the Brain Health Medicines Center at the Harrington Discovery Institute. He directs a research group focused on neuroprotection after brain injury and neurodegenerative disease.
RELATED EPISODE:
M&M 208: Glyphosate, Choline & Alzheimer’s: Toxins & Nutrition to Prevent Neurodegeneration | Ramon Velazquez
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PRACTICAL TAKEAWAYS:
Control cardiovascular health, engage in regular physical & social activity, prioritize sleep to support brain metabolic health and lower dementia risk.
Avoid excess alcohol, as even moderate intake harms brain function over time.
Maintain overall metabolic health (e.g., via exercise and diet) to reduce risk factors like obesity or diabetes that compound brain vulnerability.
SUBSCRIBER CONTENT BELOW: Reference paper + episode transcript.
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