Relationship between clinician rated amyloid status and traditional AD biomarkers in cognitively healthy older adults

Abstract

BackgroundAccumulating evidence suggests that Alzheimer’s Disease (AD) plasma biomarkers aid in screening for at‐risk individuals, tracking disease progression, and monitoring response to interventions. Plasma amyloid‐β (Aβ) and phosphorylated tau (pTau) have shown promise in predicting cerebral deposition of Aβ, while neurofilament light chain (NfL) serves as a more global marker of neurodegeneration. However, blood collection protocols often differ, and it is important to confirm the relationship between blood biomarker values and established neuroimaging markers for AD neuropathology.MethodHere, we examined which blood biomarkers could predict clinician rating of cerebral amyloid status. We leveraged available clinical, cognitive, and neuroimaging data for 140 cognitively healthy older adults (65+, mean 72 ± 6.4) who participated in the Alzheimer’s Prevention Program (APP) study and had blood specimens available. Participants were assessed by a trained clinician and neuropsychometric test battery to exclude the presence of MCI or dementia syndromes. Cerebral amyloid burden was measured by Florbetapir (18F) positron emission tomography and images were rated by three trained clinicians as “elevated” or “non‐elevated”. Biomarkers were measured in plasma collected in acid citrate dextrose (ACD) tubes using a Quanterix Simoa® HD‐X platform, and included NfL, Aβ42, Aβ40, and p‐tau181.ResultPlasma Aβ42/40 ratio was significantly lower in the “elevated” group than in the “non‐elevated” group (p < 0.001), while NfL (p =0.008) and p‐tau 181 (p = 0.001) were both significantly higher. Aβ42/40 ratio was able to discriminate the rating groups in a ROC analysis with an AUC of 0.835, significantly outperforming p‐tau 181 (AUC = 0.640) and NfL (AUC = 0.572).ConclusionDespite collecting samples with ACD rather than the traditional EDTA as an anti‐coagulant, expected group differences were observed. Our results suggest that Aβ42/40 ratio is useful in discriminating clinician‐rated elevated cerebral amyloid status, which has important implications regarding disclosure of blood biomarker results from different collection protocols in the context of AD risk.