For decades, the diagnosis of Alzheimer’s disease has been a process of exclusion, often coming too late, after irreversible damage has been done. But the ground is shifting beneath our feet. With the advent of simple blood tests, we are entering a new era of proactive neurological health. To help us understand this revolution, we are speaking with Ivan Kairatov, a biopharma expert at the forefront of Alzheimer’s research and diagnostic innovation. He joins us to discuss a landmark community study that used a blood marker to map the hidden landscape of Alzheimer’s pathology, revealing surprising insights into the interplay of age, genetics, and lifestyle, and charting the complex path toward turning this research into a clinical reality.
The study used plasma pTau217 as a surrogate marker for Alzheimer’s. Could you walk us through how this specific blood marker reflects the underlying brain pathology and explain the clinical importance of identifying an ‘intermediate’ group, which captured a significant portion of participants?
Absolutely. For a long time, we were essentially looking at shadows on a cave wall when it came to diagnosing Alzheimer’s in living patients. We needed invasive spinal taps or expensive PET scans. The pTau217 marker is a game-changer because it acts like a direct signal flare from the distressed brain. What happens is, the amyloid-β plaques start accumulating, and this triggers a downstream cascade that leads to the tangling of tau proteins inside neurons. When tau gets phosphorylated, specifically at the 217th position, it’s a very specific sign that this pathological process is underway. Some of this pTau217 leaks out of the brain and into the bloodstream, where we can now detect it with incredible sensitivity. The ‘intermediate’ category, which we defined as between 0.40 and 0.63 pg/mL, is clinically crucial. It’s not a diagnostic failure; it’s a warning sign. These are individuals who aren’t ‘negative’ but aren’t yet fully ‘positive’. This is likely the window where the disease process is smoldering, and it represents a massive opportunity for intervention before the fire really takes hold.
Your findings show a dramatic rise in Alzheimer’s changes with age, with 10% of cognitively normal adults over 70 testing positive. How should we interpret these ‘silent’ brain changes, and what does this discovery mean for an individual’s future risk of developing symptoms?
Seeing that number—10% of people over 70 walking around with no cognitive complaints but with the biological footprint of Alzheimer’s in their blood—is truly sobering. We call this the preclinical stage of the disease. It forces us to redefine Alzheimer’s not as something that begins with memory loss, but as a slow, progressive condition that can brew for a decade or more before the first symptom appears. For an individual, a positive test in this stage is not a guarantee of future dementia, but it is an undeniable elevation of risk. The best analogy is finding out you have high cholesterol. It doesn’t mean you’re having a heart attack tomorrow, but it’s a powerful, urgent call to action. It tells us that the biological clock is ticking, and it empowers us to think about risk-reduction strategies, whether that’s lifestyle changes or, in the future, early-stage therapeutics.
The study linked the APOE ε4 gene to a much higher prevalence of Alzheimer’s changes, yet a higher education level had a protective effect. Can you elaborate on this interplay and discuss how certain lifestyle factors might help mitigate a strong genetic predisposition?
This is one of the most hopeful aspects of the research. We saw a stark, dose-dependent relationship with the APOE ε4 gene; prevalence of Alzheimer’s changes jumped from 27.1% in non-carriers to a staggering 64.6% in those with two copies of the allele. It’s a powerful genetic push toward the disease. But then you see this clear, inverse association with education. Those with a tertiary education had the lowest prevalence. This speaks to the concept of ‘cognitive reserve.’ Think of your brain as a complex network of roads. A higher education, and the lifelong learning it often entails, seems to build a more intricate and robust road system with more connections and alternative routes. When Alzheimer’s starts to create roadblocks, a brain with high cognitive reserve can simply reroute traffic for longer, maintaining function even as the underlying pathology worsens. It doesn’t stop the disease, but it builds resilience against its effects, effectively delaying the onset of clinical symptoms. It shows that while genetics may load the gun, lifestyle and environment can play a crucial role in pulling the trigger.
Interestingly, reduced kidney function was linked to higher pTau217 levels, while other major diseases like cardiovascular disease were not. What is the potential biological reason for this specific connection, and how does this finding impact our approach to assessing dementia risk in older patients?
This was a fascinating and vital finding. Our kidneys are the body’s master filtration system, and that includes clearing waste products and proteins from the blood. The data showed a distinct link between higher pTau217 and reduced kidney function, particularly once the filtration rate dropped below about 51 mL/min/1.73 m². The most straightforward hypothesis is a clearance issue: if the kidneys aren’t filtering the blood efficiently, molecules like pTau217 might simply build up, giving an artificially high reading that doesn’t perfectly reflect the brain’s state. It’s a critical confounding variable. This means a clinician can’t just look at a pTau217 result in a vacuum. They must also consider the patient’s renal health. For an older patient with chronic kidney disease, an elevated pTau217 level requires a more cautious interpretation and likely more definitive follow-up testing. It’s a powerful reminder that the brain doesn’t exist in isolation; it’s part of a complex, interconnected system.
Based on your results, about 11% of the 70+ population may be eligible for new anti-amyloid therapies. What are the practical steps and major challenges involved in translating this type of population-level screening into a tool that primary care doctors can use for individual patient decisions?
The journey from a population-level estimate to a routine clinical tool is a marathon, not a sprint. Identifying that 11% of the population could be eligible is one thing; actually getting them diagnosed and treated is an enormous logistical, ethical, and educational challenge. First, we need to educate primary care physicians, who are on the front lines. They need to understand the nuances of who to screen, how to interpret the results—especially that ‘intermediate’ group—and what the appropriate next steps are. Second, we need to build the infrastructure. A positive blood test isn’t a final diagnosis; it’s a triage tool. It necessitates a clear pathway for confirmatory testing, like a PET scan, and counseling for the patient and their family. There’s also the profound emotional weight of this knowledge. How do you tell a perfectly healthy 72-year-old that they have the biology of Alzheimer’s? Managing that anxiety and providing clear, hopeful guidance is perhaps the biggest challenge of all.
What is your forecast for the future of Alzheimer’s screening and early diagnosis over the next five to ten years?
I am incredibly optimistic. Over the next decade, I believe we will see a seismic shift in how we approach brain health. I forecast that blood-based biomarker screening for Alzheimer’s will become a routine part of geriatric medicine, much like cholesterol and blood pressure checks are today for cardiovascular health. We will move away from a reactive model—waiting for devastating symptoms like memory loss—to a proactive one, where we identify risk based on biology. This will completely reframe the disease, transforming it from a terminal diagnosis into a manageable chronic condition. The conversation will shift from “You have Alzheimer’s” to “You have the early biological markers for Alzheimer’s, and here is our plan to slow it down.” This will usher in an era of prevention and early intervention that will, I hope, save millions of minds.
