Revolution at the Memory Clinic: Inside UCL’s NHS Trial of a £100 Alzheimer’s Blood Test, the 90% Accuracy Evidence, and What Comes Next

ADAPT evaluates a plasma p‑tau217 assay alongside standard cognitive assessments in NHS memory clinics. More than 1,000 participants with suspected dementia will be enrolled across 20 sites. To test the impact of timely biomarker information, result disclosure is staggered: half of participants receive blood test results within three months and the others at 12 months. Outcomes include diagnostic accuracy and time to diagnosis, the influence of the blood result on referrals to PET or CSF, changes in patient and clinician decision‑making, and quality‑of‑life measures.

The rationale is pragmatic. PET and CSF—long considered reference standards—are limited by cost, capacity, and invasiveness, and only a small fraction of patients currently access them during work‑up. As a result, many diagnoses rely on history and cognitive testing alone, with higher risk of misclassification in early disease. A scalable blood test that reflects Alzheimer’s biology could lift diagnostic certainty early in the pathway without sending most patients to PET/CSF.

The trial is designed with the therapeutic era in mind. Disease‑modifying therapies for early Alzheimer’s require evidence of amyloid‑β pathology prior to treatment. If blood biomarker testing can reliably triage who should proceed to confirmatory testing—and, in some scenarios, obviate it—the NHS can deliver faster, fairer access to treatment while conserving specialist resources. Initial ADAPT readouts are expected in around three years.

Phosphorylated tau at threonine 217 (p‑tau217) reflects the presence of amyloid‑β plaques and tau tangles—the core pathologies of Alzheimer’s disease that can accumulate long before symptoms. Modern assays often report the percentage of p‑tau217 relative to non‑phosphorylated tau ("%p‑tau217"), measured by mass spectrometry or high‑sensitivity immunoassay.

In a 2024 multicenter analysis spanning BioFINDER‑2 and the Knight ADRC, plasma %p‑tau217 was clinically equivalent to FDA‑cleared CSF tests for classifying Aβ‑PET status (AUC ~0.95–0.97) and generally superior for tau‑PET classification (AUC 0.95–0.98). Among individuals with mild cognitive impairment and mild dementia—the group most relevant for treatment decisions—%p‑tau217 delivered ~89–90% accuracy for Aβ‑PET and ~87–88% for tau‑PET, rising to ~95% with a two‑cutoff strategy that minimizes equivocal results.

These results support the target of 90%+ accuracy and underscore the need for robust assay design, calibration, and interpretation—all focus areas for ADAPT in the diverse, real‑world context of NHS clinics.

Performance in specialty cohorts must translate to everyday practice. In a prospective study of 1,213 symptomatic patients across primary and secondary care, percentage p‑tau217 alone—or combined with the Aβ42:40 ratio as the amyloid probability score 2 (APS2)—achieved AUC ~0.96–0.97 with high positive and negative predictive values across cohorts when predefined cutoffs were applied.

Crucially, clinician diagnostic accuracy improved markedly when the blood test informed decisions. In the primary care cohort, accuracy for identifying clinical Alzheimer’s after routine evaluation (history, cognitive testing, CT) was ~61%; with the blood test it rose to ~91%. Among dementia specialists, accuracy increased from ~73% to ~91% when blood biomarkers were available. These gains mean fewer misclassifications, clearer next steps, and more appropriate referrals for confirmatory testing.

For the NHS, this evidence shows that p‑tau217‑based testing is practical and impactful in routine settings. ADAPT will now test how to translate that performance into improved patient flow, shorter time to diagnosis, and better experiences for patients and carers at national scale.

Implementation hinges on clear thresholds: where a blood test alone suffices versus when confirmatory PET/CSF is needed. A 2024 multi‑cohort framework aligned interpretation with clinical pretest probability. In probable Alzheimer’s dementia, a positive p‑tau217 result can effectively rule in amyloid‑β pathology with positive predictive values above 95%. In non‑Alzheimer’s dementias, a negative result yields negative predictive values in the 90–99% range, supporting rule‑out without confirmatory testing.

Mild cognitive impairment is more nuanced. Age, phenotype, and consequences of error matter; some cases still merit confirmation. A two‑cutoff approach—defining rule‑in and rule‑out ranges with a small gray zone—can minimize unnecessary PET/CSF while maintaining safety. In practice, the NHS can deploy blood tests first, reserving confirmatory testing for equivocal blood results, atypical presentations, younger MCI patients, and cases where treatment eligibility demands definitive confirmation. ADAPT is designed to prospectively test these pathway decisions.

At roughly £100 per test, p‑tau217 is priced for scale. But delivering reliable results across sites requires standardization: harmonized cutoffs across platforms, calibration against reference methods, external proficiency testing, and clear reporting tied to pretest probability. Complementary biomarkers (Aβ42:40, neurofilament light, GFAP) and platform choices (mass spectrometry vs immunoassay) should be evaluated for added value and operational fit.

Pathways must be explicit: when to order the blood test; actions for positive, negative, and indeterminate results; and triggers for confirmatory PET/CSF irrespective of blood results. Routine audit of false positives/negatives and turnaround times should be built in.

Equity is central. Today, only a minority of patients access PET or CSF confirmation, disadvantaging those far from specialist centers. Standardized blood testing in memory clinics can democratize access to accurate diagnosis, accelerate eligibility assessments for disease‑modifying therapies, and reduce the psychological toll of prolonged uncertainty.

Recent anti‑amyloid therapies for early Alzheimer’s include US‑approved agents that require confirmation of amyloid‑β pathology prior to treatment. Amyloid PET tracers—florbetapir F‑18 (Amyvid), flutemetamol F‑18 (Vizamyl), and florbetaben F‑18 (Neuraceq)—are authorized to estimate neuritic plaque density in adults with cognitive impairment. Capacity and costs constrain their use at scale, underscoring the role for blood testing as the front door to triage: rule in high‑probability cases, rule out low‑probability cases, and route gray‑zone patients to confirmatory testing.

Blood biomarkers may also support longitudinal monitoring alongside cognition and function, a priority for future research. With ADAPT results expected in about three years, the NHS can use this window to contract validated assays, train clinics, define confirmatory criteria, integrate laboratory information systems with electronic health records, and establish audit metrics. If ADAPT confirms that blood testing lifts accuracy above 90% and improves pathways, routine adoption could follow swiftly.

Tau assembles into paired helical filaments and neurofibrillary tangles that track with symptom progression. Phosphorylation at threonine 217 correlates closely with amyloid‑associated tau pathology. Structural studies of tau filaments from Alzheimer’s brain highlight conformations consistent with disease‑specific aggregation, supporting the biological rationale for p‑tau217 as a sensitive blood marker of Alzheimer’s pathology.