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In a study of biomarkers in Alzheimer’s dementia, plasma p-tau217 had greater agreement with CSF and amyloid-PET biomarker profiles than did FDG-PET scans.

Phosphorylated tau (p-tau) 217 had greater sensitivity and overall accuracy compared with fluorodeoxyglucose-positron emission tomography (FDG-PET) scans for Alzheimer’s dementia (AD) among patients with early-onset or atypical dementia, according to study results published in Neurology.

Kely Monica Quispialaya, MD, and colleagues conducted a retrospective analysis of 81 patients with atypical or early-onset dementia assessed at a specialized memory clinic between 2018 and 2023. Patients with younger onset dementia (≤65 years), regardless of their clinical presentation, or patients with dementia (aged ≥65 years) who had behavioral or cognitive symptoms other than memory as the predominant clinical symptoms were included.

All patients underwent measurement of cerebrospinal fluid (CSF) and amyloid-PET (Aβ42, p-tau181, and total tau levels), as well as FDG-PET scans, amyloid-PET scans, and p-tau217 quantifications. The primary endpoints included sensitivity and specificity for the biomarkers.

The patients were classified according to their CSF biomarker status as non-AD (n=47; 58%) or AD (n=34; 42%). The researchers observed statistically significant differences between the two groups when comparing Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. MMSE scores were lower in the AD group than in the non-AD group (P=0.001). Researchers noted a similar pattern for MoCA scores (P=0.001) in the AD group versus the non-AD group.

Both FDG-PET and plasma p-tau217 showed high levels of agreement with reference standard AD biomarkers (FDG-PET area under the curve [AUC], 71%; plasma p-tau217 AUC, 81%). Specificity for both biomarkers was similar (FDG-PET, 70%; 95% CI, 0.56-0.81; p-tau217, 70%; 95% CI, 0.56-0.8). However, p-tau217 had higher sensitivity for AD compared with FDG-PET (p-tau217, 97%; 95% CI, 0.85-0.99 vs FDG-PET, 73%; 95% CI, 0.57-0.85, respectively; P=0.01). Overall, the researchers found that accuracy was also higher for p-tau217 versus FDG-PET (AUC=84%; 95% CI, 0.75-0.93 vs AUC=72%; 95% CI, 0.60-0.83, respectively; P=0.02).

The study team observed the same pattern of results when using amyloid-PET as the reference standard. The authors noted that the specificity of 79% for amyloid-PET positivity exhibited in their study “calls for caution for possible use in clinical practice and for determining eligibility for disease-modifying treatments for AD.”

“Among cognitively impaired individuals who meet appropriate use criteria for AD biomarker investigations, plasma p-tau217 had greater agreement with CSF and amyloid-PET biomarker profiles than did FDG-PET visual assessments. Future work should replicate these findings in secondary care settings,” the researchers concluded.