Wheelock, Muriah D;
Strain, Jeremy F;
Mansfield, Patricia;
Tu, Jiaxin Cindy;
Tanenbaum, Aaron;
Preische, Oliver;
Chhatwal, Jasmeer P;
... Xu, Xiong; + view all
(2023)
Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer’s disease.
Brain
, 146
(7)
pp. 2928-2943.
10.1093/brain/awac498.
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Abstract
Neurofilament light chain, a putative measure of neuronal damage, is measurable in blood and cerebrospinal fluid and is predictive of cognitive function in individuals with Alzheimer Disease. There has been limited prior work linking neurofilament light and functional connectivity and no prior work has investigated neurofilament light associations with functional connectivity in autosomal dominant Alzheimer Disease. Here we assessed relationships between blood neurofilament light, cognition, and functional connectivity in a cross-sectional sample of 106 autosomal dominant Alzheimer Disease mutation carriers and 76 non-carriers. We employed an innovative network-level enrichment analysis approach in order to assess connectome-wide associations with neurofilament light. Neurofilament light was positively correlated with deterioration of functional connectivity within the default mode network and negatively correlated with connectivity between default mode network and executive control networks including the cingulo-opercular, salience, and dorsal attention networks. Further, reduced connectivity within the default mode network and between the default mode network and executive control networks was associated with reduced cognitive function. Hierarchical regression analysis revealed that neurofilament levels and functional connectivity within the default mode network and between the default mode network and the dorsal attention network explained significant variance in cognitive composite scores when controlling for age, sex, and education. A mediation analysis demonstrated that functional connectivity within the default mode network and between the default mode network and dorsal attention network partially mediated the relationship between blood neurofilament light levels and cognitive function. Our novel results indicate that blood estimates of neurofilament levels correspond to direct measurements of brain dysfunction, shedding new light on the underlying biological processes of Alzheimer Disease. Further, we demonstrate how variation within key brain systems can partially mediate the negative effects of heighted total serum neurofilament levels, suggesting potential regions for targeted interventions. Finally, our results lend further evidence that low-cost and minimally invasive blood measurements of neurofilament may be a useful marker of brain functional connectivity and cognitive decline in Alzheimer disease.
| Type: | Article |
|---|---|
| Title: | Brain network decoupling with increased serum neurofilament and reduced cognitive function in Alzheimer’s disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/brain/awac498 |
| Publisher version: | https://doi.org/10.1093/brain/awac498 |
| 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: | NfL, neurodegeneration, functional connectivity, default mode network, resting state, enrichment |
| 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.ucl.ac.uk/id/eprint/10163313 |
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