Two-step blood-test strategy could resolve many 'gray zone' Alzheimer's amyloid results, study suggests

Blood tests for Alzheimer’s disease are cheaper and easier than amyloid PET brain scans, but one of the most promising markers, p-Tau217, leaves many people with an uncertain result. A study in Annals of Clinical and Translational Neurology by researchers at Boston University Chobanian & Avedisian School of Medicine and the University of Connecticut tests a step-by-step fix called GRAD (Gatekeeper-Reflex model for AD).

How it works

• Step one looks only at p-Tau217. If the result is clearly positive or negative, no further testing is needed.
• If the result falls into the gray zone, the model adds other blood biomarkers together with age and genetic risk.

The data

• GRAD was developed using 145 people with memory or thinking problems from the Alzheimer’s Disease Neuroimaging Initiative, all of whom had blood measurements and an amyloid PET scan as the reference.
• It was then tested in an independent group of 1,644 cognitively unimpaired participants from the A4/LEARN studies. Among the 630 whose p-Tau217 results were in the gray zone, GRAD improved amyloid identification and reduced the proportion who would still need PET imaging, according to the university’s summary.

Why it matters

New disease-modifying Alzheimer’s treatments require confirming brain amyloid first, and prevention trials must screen very large groups. A “test first, investigate further only when needed” approach could make that cheaper.

Limitations

The authors themselves say GRAD is not ready to replace confirmatory imaging and must be tested prospectively before routine use. The study is a retrospective analysis of existing research cohorts, the development group was small (145 people), and research volunteers may differ from typical clinic patients. The size of the improvement is reported in the paper rather than here. People worried about memory should talk to their doctor.