Racine, AM;
Merluzzi, AP;
Adluru, N;
Norton, D;
Koscik, RL;
Clark, LR;
Berman, SE;
... Johnson, SC; + view all
(2019)
Association of longitudinal white matter degeneration and cerebrospinal fluid biomarkers of neurodegeneration, inflammation and Alzheimer's disease in late-middle-aged adults.
Brain Imaging and Behavior
, 13
(1)
pp. 41-52.
10.1007/s11682-017-9732-9.
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Abstract
Alzheimer's disease (AD) is characterized by substantial neurodegeneration, including both cortical atrophy and loss of underlying white matter fiber tracts. Understanding longitudinal alterations to white matter may provide new insights into trajectories of brain change in both healthy aging and AD, and fluid biomarkers may be particularly useful in this effort. To examine this, 151 late-middle-aged participants enriched with risk for AD with at least one lumbar puncture and two diffusion tensor imaging (DTI) scans were selected for analysis from two large observational and longitudinally followed cohorts. Cerebrospinal fluid (CSF) was assayed for biomarkers of AD-specific pathology (phosphorylated-tau/Aβ42 ratio), axonal degeneration (neurofilament light chain protein, NFL), dendritic degeneration (neurogranin), and inflammation (chitinase-3-like protein 1, YKL-40). Linear mixed effects models were performed to test the hypothesis that biomarkers for AD, neurodegeneration, and inflammation, or two-year change in those biomarkers, would be associated with worse white matter health overall and/or progressively worsening white matter health over time. At baseline in the cingulum, phosphorylated-tau/Aβ42 was associated with higher mean diffusivity (MD) overall (intercept) and YKL-40 was associated with increases in MD over time. Two-year change in neurogranin was associated with higher mean diffusivity and lower fractional anisotropy overall (intercepts) across white matter in the entire brain and in the cingulum. These findings suggest that biomarkers for AD, neurodegeneration, and inflammation are potentially important indicators of declining white matter health in a cognitively healthy, late-middle-aged cohort.
| Type: | Article |
|---|---|
| Title: | Association of longitudinal white matter degeneration and cerebrospinal fluid biomarkers of neurodegeneration, inflammation and Alzheimer's disease in late-middle-aged adults |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s11682-017-9732-9 |
| Publisher version: | https://doi.org/10.1007/s11682-017-9732-9 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Biomarkers, Cerebrospinal fluid, Linear mixed effects, Longitudinal, Preclinical Alzheimer’s disease, White matter |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10066237 |
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