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

NEUROBIOLOGY OF AGING

卷:68

Article

Osborn, Katie E.¹  Liu, Dandan^1,2  Samuels, Lauren R.²  Moore, Elizabeth E.¹  Cambronero, Francis E.¹  Acosta, Lealani Mae Y.¹  Bell, Susan P.^1,3,4  Babicz, Michelle A.¹  Gordon, Elizabeth A.¹  Pechman, Kimberly R.¹  Davis, L. Taylor⁵  Gifford, Katherine A.¹  Hohman, Timothy J.¹  Blennow, Kaj⁶  Zetterberg, Henrik⁶  Jefferson, Angela L.¹ 

[1] Vanderbilt Univ, Med Ctr, Dept Neurol, Vanderbilt Memory & Alzheimers Ctr, Nashville, TN USA

[2] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA

[3] Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN USA

[4] Vanderbilt Univ, Med Ctr, Dept Med, Div Geriatr Med, Nashville, TN USA

[5] Vanderbilt Univ, Med Ctr, Radiol & Radiol Sci, Nashville, TN USA

[6] Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Sahlgrenska Acad, Molndal, Sweden

关键词: Cerebrospinal fluid;    Dementia;    White matter hyperintensities;    Amyloid;    beta-amyloid(42);    Neurofilament light;   

DOI  :  10.1016/j.neurobiolaging.2018.03.028

来源: Elsevier

【 摘 要 】

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 beta-amyloid(42) deposition (A beta(42)), 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-epsilon 4 carrier status. A beta(42) (beta = -0.001, p = 0.007) and NFL (beta = 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 A beta(42) 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. (C) 2018 Elsevier Inc. All rights reserved.

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