Plasma Alzheimer's disease markers and MRI load of vascular pathology and neurodegeneration: the SMART-MR Study

Introduction

Two of the main causes for dementia are Alzheimer's disease (AD) pathology and vascular pathology. Plasma biomarkers for AD pathology have recently emerged, including amyloid-beta, p-tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Vascular pathology can be assessed on MRI via white matter hyperintensities (WMH) and infarcts. Our aim was to estimate the relationship between plasma AD biomarkers and MRI markers of vascular pathology and neurodegeneration in non-demented individuals with manifest arterial disease.

Methods

Data from 594 individuals (mean (SD) age: 64 (8) years; 17% female) were included from the SMART-MR Study, a prospective cohort study from the UMC Utrecht in the Netherlands. Vascular and neurodegenerative MRI markers included WMH volume, presence of infarcts (yes/no), total brain volume (TBV), and hippocampal volume (HV) assessed on 1.5T MRI. AD plasma markers (amyloid-beta 42/40 ratio, ptau-181, NfL, and GFAP) were assessed using Single Molecular Array (Simoa; Quanterix) assays. Linear regressions were performed for each plasma marker with WMH volume, TBV, and HV, correcting for age, sex, education, and ICV. Additionally, logistic regressions were performed for the presence of lacunar and cortical infarcts. Plasma AD levels were converted to z-scores.

Results

Higher ptau-181 was associated with larger WMH volume (β=0.16, 95% CI=0.06; 0.26, p=0.001). Higher NfL (β=-5.63, 95% CI=-8.95; -2.31, p=0.001) was associated with lower TBV. Higher NfL levels (.R=1.58, 95% CI=1.20; 2.08, p=0.001) and higher GFAP levels (OR=1.45, 95% CI=1.09; 1.92, p=0.010) were associated with cortical infarcts.

Discussion

In our sample of patients with manifest arterial disease, NfL was related to both brain volume and infarcts. Further, an association between ptau-181 and WMH was found, as well as between GFAP and cortical infarcts. Plasma biomarkers offer the potential to easily measure a wider range of pathophysiological processes related to cognitive decline.