Can You Catch Alzheimer’s Before It Starts?

Early Detection of Alzheimer’s: The Promise of Biomarkers and Proteomic Clocks

Dr. Topol opens by highlighting one of the most exciting developments in Alzheimer’s research: the ability to detect changes in specific biomarkers, such as PTA 217, up to 20 years before the onset of mild cognitive impairment. This is a remarkable lead time that offers a critical window for prevention and intervention. PTA 217, a blood-based biomarker, has shown accuracy comparable to more invasive and expensive tests like cerebrospinal fluid analysis or PET scans, but with far greater accessibility and less risk.

The discussion emphasizes that Alzheimer’s disease, like many age-related illnesses, has a long preclinical phase. The disease process begins silently, often decades before memory loss or cognitive symptoms become apparent. This extended “runway” means that early detection through blood tests and proteomic clocks—advanced analyses of thousands of plasma proteins—can provide a detailed picture of how the brain and other organs are aging. These proteomic clocks are revolutionary because they assess biological age organ by organ, including the brain and immune system, rather than relying solely on genetic risk or epigenetic markers derived from white blood cells.

Dr. Topol stresses that while genetic factors such as the APOE4 gene increase Alzheimer’s risk, they do not guarantee disease development. His research on a unique cohort of “elderly” individuals—people aged 90 to 102 who have avoided chronic age-related diseases—revealed surprisingly little genetic determinism. Instead, lifestyle factors, immune system resilience, and perhaps some element of chance play significant roles in healthy aging. This finding challenges the common misconception that genetics alone dictate one’s fate and underscores the power of modifiable behaviors.

Lifestyle and Immune Health: The Cornerstones of Prevention

Throughout the conversation, Dr. Topol returns to the critical importance of lifestyle in preventing Alzheimer’s and other age-related diseases. He describes strength training and sleep as “powerful drugs” that outperform many pharmaceuticals in their ability to maintain health and slow biological aging. Strength training, in particular, helps preserve muscle mass and combat frailty, a major risk factor for morbidity and mortality in older adults. Sleep, especially deep slow-wave sleep, is essential for clearing toxic waste from the brain, and improving sleep quality and regularity can have profound effects on brain health.

Social connection also emerges as a vital factor. Dr. Topol cites extensive data linking social isolation to increased risk of neurodegenerative diseases, cardiovascular disease, and even cancer. The podcast highlights how positive social relationships can influence gene expression, turning off inflammatory pathways and promoting anti-inflammatory ones, while conflictual or lonely states do the opposite. This “sociogenomic” perspective reinforces the idea that mental and emotional well-being are inseparable from physical health.

Diet is another major pillar of prevention. Dr. Topol warns against ultraprocessed foods, which are highly inflammatory and prevalent in Western diets, especially in the United States. He also cautions against excessive protein intake, particularly animal protein, which may promote atherosclerosis and inflammation. Instead, he advocates for a mostly plant-based Mediterranean-style diet, which has been consistently associated with longevity and reduced risk of age-related diseases.

The Role of Genetics and Polygenic Risk Scores

While genetics are not destiny, they provide valuable information when combined with other data. Dr. Topol explains the concept of polygenic risk scores, which aggregate the effects of many common genetic variants to estimate an individual’s risk for diseases like Alzheimer’s, heart disease, and cancer. Importantly, these scores can be modulated by lifestyle factors, meaning that even those with high genetic risk can reduce their chances of disease through healthy behaviors.

The podcast also touches on rare pathogenic mutations, such as BRCA genes for cancer, which confer high risk but are relatively uncommon. Whole genome sequencing, now affordable and accessible, can identify these mutations as well as polygenic risk profiles, enabling truly personalized medicine.

Advances in Heart Disease Prevention

As a cardiologist, Dr. Topol provides a detailed update on heart disease prevention, emphasizing that despite decades of progress, cardiovascular disease remains the leading cause of death worldwide. He explains that new diagnostic tools, including polygenic risk scores, advanced lipid panels measuring apolipoprotein B and lipoprotein(a), and heart-specific proteomic clocks, allow clinicians to identify high-risk individuals long before clinical disease manifests.

He highlights emerging therapies, such as PCSK9 inhibitors and novel drugs targeting lipoprotein(a), which promise to dramatically lower cardiovascular risk in patients with genetic predispositions. Additionally, AI-driven imaging techniques, including retinal scans analyzed by machine learning, can predict heart disease and stroke risk years in advance by detecting subtle vascular changes.

Dr. Topol reiterates that lifestyle remains the most powerful preventive tool, capable of reducing cardiovascular risk by up to 90%. However, combining lifestyle with precision pharmacology and advanced diagnostics offers the best chance to prevent heart attacks and strokes.

Cancer: The New Frontier of Early Detection and Immune Surveillance

The conversation then turns to cancer, where Dr. Topol expresses optimism about the potential to transform cancer from a feared killer into a manageable or even preventable condition. He critiques current screening methods as blunt instruments that treat all individuals the same, regardless of risk, leading to overtesting and missed opportunities.

Instead, he envisions a future where polygenic risk scores, whole genome sequencing, and proteomic signatures identify who is truly at risk for specific cancers. Liquid biopsies detecting circulating tumor DNA, though currently expensive and limited in sensitivity, are rapidly improving and could enable detection of microscopic cancers long before they become visible on imaging.

AI plays a crucial role here as well, analyzing subtle patterns in routine lab tests and electronic health records to flag early signs of cancer risk that humans might miss. This approach has shown promise in detecting hard-to-diagnose cancers like pancreatic and ovarian cancer years before clinical presentation.

Dr. Topol also emphasizes the central role of the immune system in cancer prevention and treatment. He discusses advances in immunotherapy, including engineered T-cell therapies that can cure autoimmune diseases and hold promise for eradicating metastatic cancer. However, he notes that a major gap remains: the lack of routine clinical metrics to assess immune system health and function. Developing comprehensive “immunomes” that profile immune cell populations and antibody repertoires could revolutionize personalized cancer prevention and therapy.

The Convergence of Aging Science, AI, and Multimodal Medicine

A recurring theme throughout the podcast is the convergence of multiple scientific advances that make this new era of early detection and prevention possible. The science of aging has provided metrics like epigenetic and proteomic clocks that quantify biological age and organ-specific aging. AI and machine learning enable integration and interpretation of vast, complex datasets from genetics, proteomics, imaging, and clinical records. Together, these tools allow for precise, individualized risk assessment and targeted interventions.

Dr. Topol stresses that this is a historic moment in medicine, where primary prevention of the “big three” age-related diseases—Alzheimer’s, heart disease, and cancer—is finally within reach. He cautions, however, that success depends on widespread adoption of these technologies, improved physician education, and patient engagement in lifestyle changes.

Conclusion: A Hopeful Future for Alzheimer’s and Age-Related Diseases

The podcast closes on an optimistic note, with Dr. Topol expressing hope that the combination of early biomarker detection, lifestyle modification, advanced therapeutics, and AI-driven precision medicine will dramatically reduce the burden of Alzheimer’s and other age-related diseases. He encourages listeners to focus on modifiable factors like diet, exercise, sleep, and social connection while embracing new diagnostic tools when appropriate.

Ultimately, the message is clear: Alzheimer’s and other chronic diseases are not inevitable. With the right knowledge, tools, and commitment, we can catch these conditions before they start and extend not just lifespan but health span—living longer, healthier, and more vibrant lives.