In:
Alzheimer's & Dementia, Wiley, Vol. 18, No. S4 ( 2022-12)
Abstract:
Neuroinflammation is a hallmark of Alzheimer ́s disease (AD) and other neurodegenerative disorders and is likely to be triggered throughout different stages of the disease. Microglia and Astrocytes are the main resident glia that mediate neuroinflammation through production of cytokines, chemokines and other neuroinflammatory biomarkers. Inflammatory processes have been implicated in the pathogenesis of cerebrovascular disease and white matter (WM) injury. However, imaging studies on the contribution of inflammation on WM structure in the aging and AD are rare. Method Here, we aim to examine the relationship between inflammatory markers and WM hyperintensities (WMH) in the spectrum from normal aging towards AD. To do that, we used baseline data from the DZNE DELCODE study that is enriched in subjects at risk for development of AD and examined a panel of 16 inflammatory biomarkers from CSF of 249 subjects who also underwent FLAIR imaging. Participants included cognitively unimpaired (CU) individuals (healthy controls, AD relatives, and SCD) and cognitively impaired patients (CI) with MCI or AD dementia. WMH lesion volumes were automatically segmented from FLAIR images. Principal component analysis on the CSF markers generated one main composite factor (CP1) that included mainly TREM2, YKL40, AXL, Tyro3 and C1q (see Figure). Age, sex, vascular risk factors, Abeta ratio and ptau181 were used as covariates. Result Linear regression models showed that higher values of this inflammatory composite factor was related to lower global WMH (p 〈 0.01) and better memory performance (p 〈 0.01) in the whole sample. These effects were also significant when including whole brain GM volume as additional covariate. Mediation model showed that global WMH partially mediated the effect of neuroinflammation on memory performance. Conclusion These results suggest that some neuroinflammatory markers (e.g. sTyro3 and sAXL) might have a protective effect on WM structure, thus being beneficial for memory function as suggested by a recent study (Brosseron, Maass, Kleineidam et al, 2022), in which sTyro3 and sAXL were related to higher GM volume. Follow‐up analyses will aim to distinguish the effect of neuroinflammation in different clinical groups. Longitudinal studies are ultimately needed to determine whether the observed effect is “protective” or related to “brain reserve”.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2201940-6
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