Cerebrospinal fluid β-amyloid42 and neurofilament light relate to white matter hyperintensities

Abstract

White matter hyperintensities (WMHs) are associated with poorer brain health, but their pathophysiological substrates remain elusive. To better understand the mechanistic underpinnings of WMHs among older adults, this study examined in vivo cerebrospinal fluid biomarkers of β-amyloid42 deposition (Aβ42), hyperphosphorylated tau pathology (p-tau), neurodegeneration (total tau), and axonal injury (neurofilament light; NFL) in relation to log-transformed WMHs volume. Participants free of clinical stroke and dementia were drawn from the Vanderbilt Memory & Aging Project (n=148, 72±6 years). Linear regression models adjusted for age, sex, race/ethnicity, education, intracranial volume, modified Framingham Stroke Risk Profile (excluding points assigned for age), cognitive diagnosis, and APOE-ε4 carrier status. Aβ42 (β=−0.001, p=0.007) and NFL (β=0.0003, p=0.01) concentrations related to WMHs, but neither p-tau nor total tau associations with WMHs reached statistical significance (p-values>0.21). In a combined model, NFL accounted for 3.2% of unique variance in WMHs and Aβ42 accounted for an additional 4.3% beyond NFL, providing novel evidence of the co-occurrence of at least two distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.

The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data

“…Prior literature has linked greater WMH to reduced verbal episodic memory performance in cognitively normal older adults [35], consistent with the current results. The NFL association in cognitively normal participants represents a novel finding but is in line with previous research linking NFL and WMH [17, 36, 37]. Collectively, these results might represent age-related changes given that WMH burden increases with age [38] and is associated with age-related decline in verbal episodic memory [39].…”

Levels of plasma neurofilament light chain and cognitive function in patients with Alzheimer or Parkinson disease

“…In addition to higher levels of periventricular and deep WML in PDD patients compared with PDND patients, the reduction of gray matter volume (GMV) over frontal-limbic-temporal regions might contribute to the higher NFL levels in PDD patents 32 , 33 . Although the paper did not show the association between the WMLs and plasma NFL level in AD patients 1 , some other papers reported that the NFL levels related to WML 34 . The reason increased NFL in cognitively impaired PD patients could be either increased WML or reduced GMV over frontal-limbic-temporal regions.…”

Longitudinal cerebrospinal fluid biomarker trajectories along the Alzheimer's disease continuum in the BIOMARKAPD study

“…The pattern of tau is different from the pattern on NfL, which increased in all groups independently of the diagnosis. NfL is found in largecaliber axons in the brain [37] and therefore has been proposed as a marker of axonal degeneration and white-matter damage in AD [38,39]. In cross-sectional studies higher levels of NfL are associated with higher risk of progression to AD dementia in MCI [40].…”