This is an excellent, timely overview! Blood-based biomarkers are finally making Alzheimer’s biology clinically scalable, not just academically interesting.
A few physician-scientist reflections that feel worth highlighting for our longevity-focused readers:
1. The real breakthrough is triage. Plasma p-tau species (especially p-tau217/181) and the Aβ42/40 ratio are increasingly useful for identifying who is likely to have underlying AD pathology and who may not, helping us reserve PET/CSF for the patients where it will actually change management. This is how we reduce “diagnostic wandering” while expanding access.
2. Context and pretest probability matter as much as the assay. In a low-risk, minimally symptomatic population, even a strong test can yield confusing positives; in an appropriate clinical context (progressive cognitive syndrome, strong family history, APOE4, etc.), these markers become far more actionable. Biomarkers should support the diagnosis, not replace the clinical story.
3. Think in panels, not single numbers. p-tau (AD-type tau pathology), Aβ42/40 (amyloid biology), and markers like NfL/GFAP (neuroaxonal injury/glial activation) answer different questions. Interpreting them together helps distinguish “AD pathology likely” from “brain injury is happening” from “something inflammatory/vascular/other may be driving symptoms.”
4. The ethics are huge. If we’re moving toward earlier detection, we owe patients clear counseling: what a positive result does (and doesn’t) mean, what downstream confirmatory testing is appropriate, and what evidence-based risk reduction steps are worth prioritizing today (vascular risk control, sleep/hearing, exercise, depression treatment, cognitive engagement).
Blood biomarkers won’t “solve” Alzheimer’s, but they can make the diagnostic pathway more precise, more equitable, and less invasive. Thank you for translating a fast-moving field into a practical framework without hype.
Thank you for the breakdown. Blood biomarkers show the biology early, but this also means we could focus on lifestyle and resilience before symptoms appear!
Thank you for this clear breakdown of AUC, PPV, and NPV as it relates to p-tau 217. Super helpful.
This is an excellent, timely overview! Blood-based biomarkers are finally making Alzheimer’s biology clinically scalable, not just academically interesting.
A few physician-scientist reflections that feel worth highlighting for our longevity-focused readers:
1. The real breakthrough is triage. Plasma p-tau species (especially p-tau217/181) and the Aβ42/40 ratio are increasingly useful for identifying who is likely to have underlying AD pathology and who may not, helping us reserve PET/CSF for the patients where it will actually change management. This is how we reduce “diagnostic wandering” while expanding access.
2. Context and pretest probability matter as much as the assay. In a low-risk, minimally symptomatic population, even a strong test can yield confusing positives; in an appropriate clinical context (progressive cognitive syndrome, strong family history, APOE4, etc.), these markers become far more actionable. Biomarkers should support the diagnosis, not replace the clinical story.
3. Think in panels, not single numbers. p-tau (AD-type tau pathology), Aβ42/40 (amyloid biology), and markers like NfL/GFAP (neuroaxonal injury/glial activation) answer different questions. Interpreting them together helps distinguish “AD pathology likely” from “brain injury is happening” from “something inflammatory/vascular/other may be driving symptoms.”
4. The ethics are huge. If we’re moving toward earlier detection, we owe patients clear counseling: what a positive result does (and doesn’t) mean, what downstream confirmatory testing is appropriate, and what evidence-based risk reduction steps are worth prioritizing today (vascular risk control, sleep/hearing, exercise, depression treatment, cognitive engagement).
Blood biomarkers won’t “solve” Alzheimer’s, but they can make the diagnostic pathway more precise, more equitable, and less invasive. Thank you for translating a fast-moving field into a practical framework without hype.
Thank you for the breakdown. Blood biomarkers show the biology early, but this also means we could focus on lifestyle and resilience before symptoms appear!
I’d like to quote this in my talk this week!