To report the positivity rates of plasma beta amyloid 42/40 (Abeta42/40) and ptau-217 and their combination in the evaluation of patients with possible Alzheimer’s disease (AD) in a real-world national reference laboratory setting.

Recent advances in utilizing plasma biomarkers to assess AD pathology have provided new tools for evaluating patients with cognitive impairment. With the emergence of anti-amyloid therapies, efficient diagnostic evaluation is needed to identify treatment candidates accurately. We report likelihood scores from combined plasma biomarker testing at a national laboratory.

Over 4,900 patients were evaluated consecutively for plasma Abeta42/40 status using LC-MS/MS and ptau-217 via immunoassay in a high complexity CLIA-accredited laboratory. A likelihood score of beta amyloid PET positivity was derived from the combination of Abeta42/40 and ptau-217. The categorization of the calculated score was compared to that of the individual biomarkers.

58% of patients were female, in line with the higher prevalence of Alzheimer’s disease in women. All patients were above age 60 and the mean age of patients studied was 75.9 (+7.5) years. The combined use of Abeta42/40 and ptau-217 with two cutpoints resulted in a model identifying 27% of patients as having a high likelihood of positive beta amyloid PET status, while 54% was categorized as having a low likelihood and 19% as indeterminant. For the individual biomarkers, 36.5% and 37.6% of patients tested negative for Abeta 42/40 and ptau-217, respectively.  Abeta42/40 had an indeterminant rate of 44%. Ptau-217 had a positivity rate of 62% using a very sensitive cut point. All positivity rates increased with age.

In a real-world setting, combining plasma biomarkers Abeta42/40 and ptau-217 shows performance in alignment with previously reported likelihood rates. Importantly, these data suggest that combination of Abeta42/40 and ptau-217 together may be efficient in screening these patients in a real-world setting.