Electronic health records to test multimorbidity influences to plasma biomarker interpretation for Alzheimer’s disease
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Objective
Plasma biomarkers of Alzheimer’s disease (AD) pathology are frequently tested in specialized research settings, limiting generalizability of findings. Using electronic health records and banked plasma, we evaluated plasma biomarkers – phosphorylated tau 217 (p-tau 217 ), β-amyloid 1-42/1-40 (Aβ 42 /Aβ 40 ) and p-tau 217 /Aβ 42 – in a real-world, diverse clinical population with multimorbidities.
Methods
Participants (n=617; 44% Black/African American; 41% female) were selected from the University of Pennsylvania Medicine BioBank with plasma assayed using Fujirebio Lumipulse. International Classification of Diseases (ICD) Ninth and Tenth Revision codes determined AD dementia (ADD; n=43), mild-cognitive impairment (MCI; n=140), unspecified/non-AD cognitive impairment (CI; n=106), and cognitively normal cases (n=328), and other medical histories. APOE ε4, body mass index (BMI), metrics of kidney function ( e.g. , eGFR), and liver disease were derived from electronic health records. Multivariable models identified factors related to plasma levels. Previously established cutpoints classified AD status (“AD+”, “AD-”, or “Intermediate”).
Results
Plasma p-tau 217 /Aβ 42 had the strongest association with known AD-related factors – MCI, ADD, future progression to MCI/ADD, age, and APOE ε4 – compared to p-tau 217 and Aβ 42 /Aβ 40 . Plasma p-tau 217 /Aβ 42 was also associated with eGFR, diabetes, and history of hearing loss. Importantly, AD-related factors were most frequent/severe for AD+ classification by p-tau 217 /Aβ 42 , while medical morbidities were most frequent/severe for Intermediate classification. Exploratory analyses test p-tau 217 /Aβ 42 adjusted for eGFR to eliminate its influence on plamsa levels.
Interpretation
In this real-world dataset, we identified effects of multimorbidities on plasma biomarkers, especially kidney function. The p-tau 217 /Aβ 42 ratio had low rates of Intermediate classification and may help to account for multimorbidity effects on plasma levels.
