Plasma β-Amyloid Levels Associated With Structural Integrity Based on Diffusion Tensor Imaging in Subjective Cognitive Decline: The SILCODE Study.

Xiaoni Wang,Li Lin,Ying Han,Mingyan Zhao

doi:10.3389/fnagi.2020.592024

Abstract

Background: Accumulating evidence has demonstrated that plasma β-amyloid (Aβ) levels are useful biomarkers to reflect brain amyloidosis and gray matter structure, but little is known about their correlation with subclinical white matter (WM) integrity in individuals at risk of Alzheimer's disease (AD). Here, we investigated the microstructural changes in WM between subjects with low and high plasma Aβ levels among individuals with subjective cognitive decline (SCD).Methods: This study included 142 cognitively normal individuals with SCD who underwent a battery of neuropsychological tests, plasma Aβ measurements, and diffusion tensor imaging (DTI) based on the Sino Longitudinal Study on Cognitive Decline (SILCODE). Using tract-based spatial statistics (TBSS), we compared fractional anisotropy (FA), and mean diffusivity (MD) in WM between subjects with low (N = 71) and high (N = 71) plasma Aβ levels (cut-off: 761.45 pg/ml for Aβ40 and 10.74 pg/ml for Aβ42).Results: We observed significantly decreased FA and increased MD in the high Aβ40 group compared to the low Aβ40 group in various regions, including the body, the genu, and the splenium of the corpus callosum; the superior longitudinal fasciculus; the corona radiata; the thalamic radiation; the external and internal capsules; the inferior fronto-occipital fasciculus; and the sagittal stratum [p < 0.05, familywise error (FWE) corrected]. Average FA values were associated with poor performance on executive and memory assessments. No significant differences were found in either MD or FA between the low and high Aβ42 groups.Conclusion: Our results suggest that a correlation exists between WM integrity and plasma Aβ40 levels in individuals with SCD.

Highlights

Extracellular β-amyloid (Aβ) accumulation and intracellular tau deposition are the core features of Alzheimer’s disease (AD; Jack et al, 2018)
We observed significantly decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in the high Aβ40 group compared to the low Aβ40 group in various regions, including the body, the genu, and the splenium of the corpus callosum; the superior longitudinal fasciculus; the corona radiata; the thalamic radiation; the external and internal capsules; the inferior fronto-occipital fasciculus; and the sagittal stratum [p < 0.05, familywise error (FWE) corrected]
Our results suggest that a correlation exists between white matter (WM) integrity and plasma Aβ40 levels in individuals with subjective cognitive decline (SCD)

Summary

Introduction

Extracellular β-amyloid (Aβ) accumulation and intracellular tau deposition are the core features of Alzheimer’s disease (AD; Jack et al, 2018). Amyloid pathology is defined as the initiating step of AD, which leads to subsequent tau deposition and neurodegeneration (Long and Holtzman, 2019); the well-established and validated biomarkers for brain amyloidosis detection, including cerebrospinal fluid (CSF) analysis and amyloid PET, are expensive, invasive, and difficult to implement on a large scale in clinical practice (Sperling et al, 2011, 2014; Dubois et al, 2014; Honig et al, 2018). Accumulating evidence has demonstrated that plasma β-amyloid (Aβ) levels are useful biomarkers to reflect brain amyloidosis and gray matter structure, but little is known about their correlation with subclinical white matter (WM) integrity in individuals at risk of Alzheimer’s disease (AD). We investigated the microstructural changes in WM between subjects with low and high plasma Aβ levels among individuals with subjective cognitive decline (SCD)

Objectives

Methods

Results

Discussion

Conclusion