eprintid: 10057923 rev_number: 20 eprint_status: archive userid: 608 dir: disk0/10/05/79/23 datestamp: 2018-10-09 12:15:53 lastmod: 2021-09-20 22:21:45 status_changed: 2018-10-09 12:15:53 type: article metadata_visibility: show creators_name: Osborn, KE creators_name: Liu, D creators_name: Samuels, LR creators_name: Moore, EE creators_name: Cambronero, FE creators_name: Acosta, LMY creators_name: Bell, SP creators_name: Babicz, MA creators_name: Gordon, EA creators_name: Pechman, KR creators_name: Davis, LT creators_name: Gifford, KA creators_name: Hohman, TJ creators_name: Blennow, K creators_name: Zetterberg, H creators_name: Jefferson, AL title: Cerebrospinal fluid β-amyloid₄₂ and neurofilament light relate to white matter hyperintensities ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: Cerebrospinal fluid, Dementia, White matter hyperintensities, Amyloid, β-amyloid₄₂, Neurofilament light note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. 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. date: 2018-08 date_type: published publisher: ELSEVIER SCIENCE INC official_url: https://doi.org/10.1016/j.neurobiolaging.2018.03.028 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1553517 doi: 10.1016/j.neurobiolaging.2018.03.028 language_elements: English lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Zetterberg, Henrik actors_name: Harriot, Anne-Marie actors_id: HZETT94 actors_id: AHARA72 actors_role: owner actors_role: impersonator full_text_status: public publication: Neurobiology of Aging volume: 68 pagerange: 18-25 pages: 8 issn: 0197-4580 citation: Osborn, KE; Liu, D; Samuels, LR; Moore, EE; Cambronero, FE; Acosta, LMY; Bell, SP; ... Jefferson, AL; + view all <#> Osborn, KE; Liu, D; Samuels, LR; Moore, EE; Cambronero, FE; Acosta, LMY; Bell, SP; Babicz, MA; Gordon, EA; Pechman, KR; Davis, LT; Gifford, KA; Hohman, TJ; Blennow, K; Zetterberg, H; Jefferson, AL; - view fewer <#> (2018) Cerebrospinal fluid β-amyloid₄₂ and neurofilament light relate to white matter hyperintensities. Neurobiology of Aging , 68 pp. 18-25. 10.1016/j.neurobiolaging.2018.03.028 <https://doi.org/10.1016/j.neurobiolaging.2018.03.028>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10057923/1/Zetterberg_Cerebrospinal%20fluid%20%CE%B2-amyloid%E2%82%84%E2%82%82%20and%20neurofilament%20light%20relate%20to%20white%20matter%20hyperintensities_AAM.pdf