Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies

Abstract

Introduction: Patients with dementia with Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate plasma biomarkers of AD and their association with positron emission tomography (PET) biomarkers of amyloid and tau deposition in the continuum of DLB, starting from prodromal stages of the disease.

Methods: The cohort included patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), mild cognitive impairment with Lewy bodies (MCI-LB), or DLB, with a concurrent blood draw and PET scans.

Results: Abnormal levels of plasma glial fibrillary acidic protein (GFAP) were found at the prodromal stage of MCI-LB in association with increased amyloid PET. Abnormal levels of plasma phosphorylated tau (p-tau)-181 and neurofilament light (NfL) were found at the DLB stage. Plasma p-tau-181 showed the highest accuracy in detecting abnormal amyloid and tau PET in patients with DLB.

Discussion: The range of AD co-pathology can be detected with plasma biomarkers in the DLB continuum, particularly with plasma p-tau-181 and GFAP.

Keywords: Alzheimer's disease; Lewy body; PET biomarkers; REM sleep behavior disorder; mild cognitive impairment; plasma biomarkers.

FIGURE 1

Concentrations of plasma biomarkers in the DLB continuum and controls. Aβ, amyloid beta; CU, cognitively unimpaired; DLB, dementia with Lewy bodies; GFAP, glial fibrillary acid protein; iRBD, isolated rapid eye movement (REM) sleep behavior disorder; NfL, neurofilament light; MCI‐LB, mild cognitive impairment with Lewy bodies; p‐tau, phosphorylated tau.

FIGURE 2

Associations of plasma biomarkers with amyloid and tau PET biomarkers. (A, B) Scatterplots of the correlations of plasma biomarkers with PiB SUVr and ¹⁸F‐Flortaucipir SUVr. (C, D) Voxel‐based analysis of the regional associations of plasma biomarkers with PiB and ¹⁸F‐Flortaucipir SUVr. Maps are displayed at the p < 0.05 level with the t‐values displayed in the color bar. Correction for multiple comparisons was applied with false discovery rate error correction. CU, cognitively unimpaired; DLB, dementia with Lewy bodies; GFAP, glial fibrillary acid protein; iRBD, isolated rapid eye movement (REM) sleep behavior disorder; NfL, neurofilament light; MCI‐LB, mild cognitive impairment with Lewy bodies; PiB, Pittsburgh compound B; p‐tau, phosphorylated tau; SUVR, standardized uptake value ratio.

FIGURE 3

Interaction of PiB and ¹⁸Flortaucipir SUVr in the prediction of plasma p‐tau‐181. Data were stratified by (A) PiB SUVR and (B) ¹⁸Flortaucipir SUVR, which were stratified according to the first quartile, which indicated low Aβ or tau PET uptake, and to the third quartile, which indicates high Aβ or tau PET uptake. PiB, Pittsburgh compound B; pTau, phosphorylated tau; SUVR, standardized uptake value ratio.

FIGURE 4

Performance of plasma biomarkers in identifying PET biomarkers positivity. Graphs show receiver‐operating characteristic (ROC) curves of each plasma biomarker for the discrimination of (A) A+ vs A– cases, (B) T+ vs T– cases, and (C) A+T+ vs A–T– cases. Aβ, amyloid beta; GFAP, glial fibrillary acid protein; NfL, neurofilament light; p‐tau, phosphorylated tau.