| Autor: |
Wheelock, Muriah D., Strain, Jeremy F., Ances, Beau M., Preische, Oliver, Morris, John C., Bateman, Randall J., Jucker, Mathias, Benzinger, Tammie L.S., Eggebrecht, Adam T., Gordon, Brian A. |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2020 Supplement S11, Vol. 16 Issue 11, p1-4, 4p |
| Abstrakt: |
Background: Alzheimer disease is characterized by accrual of amyloid‐b and tau, cortical thinning, and disruptions in brain connectivity. Recent reports suggest neurofilament light chain (NfL), a measure of brain damage and atrophy, is measurable in the blood and is predictive of presymptomatic cognitive decline in individuals with autosomal dominant Alzheimer Disease. We sought to investigate the relationship between serum blood estimates of NfL and functional brain connectivity. We hypothesized that increasing NfL levels would be associated with increasing disruption of within and between network connectivity. Method: We performed neuroimaging and blood serum NfL assessments in a longitudinal sample of 78 mutation non‐carriers (NC) and 112 mutation carriers (MC) age 20‐65 enrolled in the Dominantly Inherited Alzheimer Network. Serum blood samples were collected and assayed in duplicate for NfL. Resting state‐functional MRI (rs‐fMRI) data were acquired on 3T Siemens scanners. For each subject, five minutes of low‐motion rs‐fMRI data were included (scrubbing with FD <0.2 mm). Functional connectivity (FC) was estimated using zero‐lag Pearson correlations calculated between 246 regions of interest (Figure 1A). NfL values were compared between mutation carriers and non‐carriers using non‐parametric Mann‐Whitney U tests (Figure 1B). We examined associations between FC and NfL using a Network Level Analysis (NLA) approach. Briefly, NLA uses non‐parametric test statistics and permutation testing to determine FC networks associated with NfL scores (Figure 1A). Result: NfL was correlated with a wide‐range of within and between‐network connectivity in MC but not NC subjects (Figure 2A). The five strongest associations with NfL were within the DMN, cingulo opercular (CO) and dorsal attention (DAN) networks. Specifically, greater levels of NfL were associated with reduced magnitude of within‐ and between‐network connectivity (Figure 2D&E). Conclusion: Only in the MC group was NfL correlated with deterioration of the DMN and reduced connectivity between the DMN and other brain systems. Reduced connectivity between DMN and CO and DAN with increasing atrophy may be associated with executive and cognitive decline following full progression to Alzheimer's disease. The present study suggests that indirect measurement of cell death and brain atrophy with serum NfL corresponds to reduced functional connectivity in presymptomatic Alzheimer's disease. [ABSTRACT FROM AUTHOR] |
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