Plasma p-tau217, a blood test increasingly used to flag or rule out Alzheimer's disease amyloid pathology, disagreed with confirmatory PET scans or spinal fluid testing in 8.5% of patients at Mayo Clinic, according to a study published in Neurology. Researchers led by Gregory S. Day and colleagues at Mayo Clinic identified specific patient-level factors, including kidney function, body mass index, sleep apnea and disease stage, that were statistically associated with these mismatched results. The study matters because the blood test is now being used in real-world clinics to help decide who may be eligible for newer anti-amyloid drugs, decisions that depend on the test correctly reflecting a patient's amyloid status. The retrospective study included 706 participants enrolled in Mayo Clinic memory and aging research studies, with a median age of 70 and 54% men. Each person had a plasma p-tau217 result classified as positive or negative by established cutoffs, which researchers then compared against amyloid PET scans and CSF p-tau181/amyloid-beta42 ratios, the two reference standards currently used to confirm Alzheimer's pathology. Among the 706 participants, 60 (8.5%) had plasma results that did not match these reference tests; false negatives, where the blood test read negative despite confirmed amyloid pathology, occurred in 5.6% of patients, significantly more often than false positives, which occurred in 2.8% (p = 0.007). Patients with false-negative results were more likely to be earlier in the disease course, measured by a milder global Clinical Dementia Rating score and higher Mini-Mental State Examination scores, and were also more likely to have obstructive sleep apnea. After adjusting for age, the researchers found that higher body mass index (odds ratio 1.14 per unit), better kidney function measured by estimated glomerular filtration rate (odds ratio 1.63 per 10 mL/min/1.73 m2), and earlier clinical stage were each independently associated with false-negative results, consistent with the idea that how the body produces, clears or dilutes the protein in blood can shift a reading away from what is actually happening in the brain. Overall discordance, combining both false positives and false negatives, was also linked to older age and obstructive sleep apnea across the full group. The authors describe the pattern as reflecting known biology: earlier-stage disease produces less of the signal to begin with, while kidney clearance and body size affect how much of the protein circulates in blood regardless of brain pathology.