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Neurobiol Aging. 2018 Aug;68:18-25. doi: 10.1016/j.neurobiolaging.2018.03.028. Epub 2018 Apr 3.

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

Author information

1
Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
2
Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
3
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
4
Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Divisions of Cardiovascular and Geriatric Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
5
Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
6
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
7
Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: angela.jefferson@vanderbilt.edu.

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, 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 hyperphosphorylated 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 2 distinct pathways for WMHs among older adults, including amyloid deposition and axonal injury.

KEYWORDS:

Amyloid; Cerebrospinal fluid; Dementia; Neurofilament light; White matter hyperintensities; β-amyloid(42)

PMID:
29702372
PMCID:
PMC6085839
[Available on 2019-08-01]
DOI:
10.1016/j.neurobiolaging.2018.03.028
[Indexed for MEDLINE]

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