Profiling of plasma biomarkers in the context of memory assessment in a tertiary memory clinic.

ABSTRACT

Plasma biomarkers have shown promising performance in research cohorts in discriminating between different stages of Alzheimer's disease (AD). Studies in clinical populations are necessary to provide insights on the clinical utility of plasma biomarkers before their implementation in real-world settings. Here we investigated plasma biomarkers (glial fibrillary acidic protein (GFAP), tau phosphorylated at 181 and 231 (pTau181, pTau231), amyloid ß (Aß) 42/40 ratio, neurofilament light) in 126 patients (age = 65 ± 8) who were admitted to the Clinic for Cognitive Disorders, at Karolinska University Hospital. After extensive clinical assessment (including CSF analysis), patients were classified as mild cognitive impairment (MCI) (n = 75), AD (n = 25), non-AD dementia (n = 16), no dementia (n = 9). To refine the diagnosis, patients were examined with [18F]flutemetamol PET (Aß-PET). Aß-PET images were visually rated for positivity/negativity and quantified in Centiloid. Accordingly, 68 Aß+ and 54 Aß- patients were identified. Plasma biomarkers were measured using single molecule arrays (SIMOA). Receiver-operated curve (ROC) analyses were performed to detect Aß-PET+ using the different biomarkers. In the whole cohort, the Aß-PET centiloid values correlated positively with plasma GFAP, pTau231, pTau181, and negatively with Aß42/40 ratio. While in the whole MCI group, only GFAP was associated with Aß PET centiloid. In ROC analyses, among the standalone biomarkers, GFAP showed the highest area under the curve discriminating Aß+ and Aß- compared to other plasma biomarkers. The combination of plasma biomarkers via regression was the most predictive of Aß-PET, especially in the MCI group (prior to PET, n = 75) (sensitivity = 100%, specificity = 82%, negative predictive value = 100%). In our cohort of memory clinic patients (mainly MCI), the combination of plasma biomarkers was sensitive in ruling out Aß-PET negative individuals, thus suggesting a potential role as rule-out tool in clinical practice.