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

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.

Heterogeneity in subjective cognitive decline in the Sino Longitudinal Study on Cognitive Decline(SILCODE): Empirically derived subtypes, structural and functional verification

“…5 Associative fiber tract neurodegeneration in the WM of AD may arise from GM atrophy and Wallerian degeneration. 41 Noting that lower FA values were only found in the neuropsychiatric SCD group, the result was consistent with previous SCD studies which specify that the SCD group exhibited lower FA values compared with the NC group. Therefore, we speculate that the outcomes indicate that the NPSs may enhance and accelerate AD pathology.…”

“…The neuropsychiatric SCD group showed lower GM volume and FA values and higher ALFF values than the NC group, which were similar to pervious SCD studies 5 . Associative fiber tract neurodegeneration in the WM of AD may arise from GM atrophy and Wallerian degeneration 41 . Noting that lower FA values were only found in the neuropsychiatric SCD group, the result was consistent with previous SCD studies which specify that the SCD group exhibited lower FA values compared with the NC group.…”

β-Amyloid in blood neuronal-derived extracellular vesicles is elevated in cognitively normal adults at risk of Alzheimer’s disease and predicts cerebral amyloidosis

“…Previously, 458 subjects in the SILCODE project underwent plasma Aβ quantification; their clinical characteristics are displayed in Additional file 1 : Table S3, and some results have been disclosed [ 26 ]. Among these, 81 Aβ− NCs, 45 Aβ+ NCs, 34 subjects with aMCI, and 20 subjects with ADD were included in the current nEV study.…”

Progress in blood biomarkers of subjective cognitive decline in preclinical Alzheimer's disease

“…[ 32 ] Plasma Aβ40 levels can reflect central nervous degeneration and may represent a valuable biomarker for predicting different aging trajectories in patients with SCD. [ 33 ] Verberk et al [ 34 ] found that the plasma Aβ42/40 ratio has the potential to serve as a pre-screening index for identifying the earliest pathological changes in AD continuity among individuals with SCD and normal cognition. The plasma Aβ42/40 ratio combined with age and APOE ε4 status yielded >80% accuracy.…”

“…The change in plasma Aβ concentration is time-dependent, and the change in hyperphosphorylated tau (hyper P-tau) protein level is parallel to the clinical progress of MCI [32] . Plasma Aβ40 levels can reflect central nervous degeneration and may represent a valuable biomarker for predicting different aging trajectories in patients with SCD [33] . Verberk et al [34] found that the plasma Aβ42/40 ratio has the potential to serve as a pre-screening index for identifying the earliest pathological changes in AD continuity among individuals with SCD and normal cognition.…”