2025 American Academy of Neurology Abstract Website

Objective:

Evaluate the performance of emerging Alzheimer disease (AD) plasma biomarkers in a specialty memory clinic.

Background:

Plasma measures of Aβ42/40 and pTau217 represent promising, accessible alternatives to “gold standard” metrics of cerebral amyloidosis in research cohorts; however, their performance in heterogeneous clinical cohorts is not yet established.

Design/Methods:

Plasma Aβ42/40 and pTau217 concentrations (Fujirebio Lumipulse) were measured in patients evaluated within a tertiary memory clinic. Syndromic and etiologic diagnoses were established by consensus, integrating clinical data and findings from MRI (n=484), FDG-PET (n=117), and CSF AD biomarkers (n=440). Performance of plasma biomarkers was evaluated using pre-established cutoffs optimized for prediction of amyloid pathology based on amyloid-PET.

Results:

Plasma AD biomarkers were measured in 509 patients (mean 68.6±9.3 years; 47% female; 91.3% non-Hispanic White), including patients with typical amnestic AD (n=235, 46.2%), non-amnestic presentations of AD (n=50, 9.8%), and non-AD causes of cognitive concerns (n=224, 44.0%). Positive plasma AD biomarkers were strongly associated with symptomatic AD (OR 95%CI; Aβ42/40≤0.0777: 3.8, 1.8-8.0; pTau217≥0.325 pg/mL: 25.0, 15.6-40.2) and CSF markers (elevated ptau181/Aβ42) of cerebral amyloidosis (Aβ42/40: 5.0, 1.7-14.3; pTau217: 42.4, 22.8-79.1). Using a 2 cutpoint model to classify results as positive, negative or intermediate; sensitivity, specificity, and predictive values (positive/negative) for plasma pTau217 were 95%, 85%, 87% and 92% when compared to AD diagnosis and 93%, 91%, 94% and 87% when compared to CSF AD biomarkers. Estimated glomerular filtration rate <60 mL/min/1.73 m² associated with elevated plasma pTau217 in CSF AD-negative patients (mean difference, 95%CI: 0.265 pg/mL, 0.150-0.379).

Conclusions:

Plasma ptau217, but not AB42/40, was strongly associated with symptomatic AD diagnoses and CSF AD biomarkers. These findings support the use of plasma ptau217 in heterogeneous clinical cohorts including patients with multiple common causes of dementia. Caution is advised in the interpretation of pTau217 results in patients with decreased renal function, due to potential elevations in plasma.