Plasma biomarkers of Alzheimer’s disease in dementia with Lewy bodies

Abstract

AbstractBackgroundAlzheimer’s disease (AD) co‐pathology is a common feature in dementia with Lewy bodies (DLB) and associated with a more rapid decline. Here, we aimed to evaluate plasma biomarkers as alternatives for CSF biomarkers for the detection of amyloid pathology, and for their diagnostic and prognostic value in DLB.MethodPlasma Aβ42/40, GFAP, NfL, pTau181 and pTau231, were measured by SIMOA in patients with DLB (n = 342), AD (n = 131), and healthy controls (n = 89) from the E‐DLB consortium cohort. Associations of biomarkers with CSF Aβ42 status were assessed with ANCOVA corrected for age and sex. ROC analyses were performed to assess biomarker’s performance for amyloid detection and differential diagnosis. Associations of biomarkers with cognitive impairment and decline were determined by linear regression and mixed effects models.ResultAltered Aβ42/40 (β = ‐0.0076, 95%CI:‐0.0137 to ‐0.0016, p<.05), pTau181 (β = 0.2503, 95%CI: 0.0555 to 0.4451, p<.05) and pTau231 levels (β = 0.2269, 95%CI:0.0347 to 0.4191, p<.05) were associated with amyloid pathology in DLB, as assessed by CSF Aβ42. The combination of these biomarkers differentiated amyloid normal from abnormal DLB patients with an AUC of 0.728 (sensitivity = 64.6%, specificity = 75.0%). pTau181 best differentiated these groups as a single marker (AUC = 0.700, sensitivity = 62.5%, specificity = 73.1%). The combination of Aβ42/40, NfL and pTau231 differentiated DLB from AD with an AUC of 0.726 (sensitivity = 73.3%, specificity = 68.8%). In DLB, increased GFAP (β = ‐8.9, 95%CI:‐11.7 to ‐6.1, p<.001), NfL (β = ‐7.2, 95%CI:‐10.0 to ‐4.4, p<.001), pTau181 (β = ‐2.6, 95%CI:‐4.0 to ‐1.2, p<.001) and pTau231 (β = ‐2.4, 95%CI:‐3.7 to ‐1.2, p<.001) were associated with lower baseline MMSE scores and increased GFAP (annual change of ‐2.1 MMSE points (95%CI:‐2.9 to ‐1.3, p<.001) and NfL (annual change of ‐2.1 MMSE points (95%CI:‐3.0 to ‐1.3, p<.001) predicted faster cognitive decline.ConclusionPlasma Aβ42/40, pTau181 and pTau231 were associated with amyloid abnormality in DLB. Their utility for differential diagnosis and identifying amyloid pathology in DLB was modest. Our findings suggest a prognostic value of GFAP and NfL for cognitive decline in DLB.