In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S5 ( 2020-12)
Kurzfassung:
Autopsy studies reported that the locus coeruleus (LC) is one of the initial regions to accumulate tau early in life. With every increase in Braak stage, LC volumes declines with approximately 8%. In addition, animal studies have reported a sexual differentiation of the locus coeruleus (LC), reflecting a higher number of neurons in women. Given the reported sexual dimorphism in subcortical volumes and cortical tau deposition, indicating a higher vulnerability in women, we sought to examine age and sex‐differences along the rostro‐caudal axis of the LC by using dedicated novel structural ultra‐high field imaging methods. Method Inclusion: 89 participants 20‐85 yrs (45F/41M,Age females 49(sd19.29), males 51(sd22.2) p=0.65). Imaging was done at 7T, including MP2RAGE anatomical scans and our previously validated MT‐TFL sequence that enables imaging the length of the LC at 0,4mm 3 . Structural scans were bias‐field corrected and we generated a common template using an iterative diffeomorphic warp estimate with Advanced Normalization Tools (ANTs http://stnava.github.io/ANTs/) and LC templates were constructed by manual tracing the average projection map (RWEvH, Figure 1A). The segmented LC was then projected to each high‐resolution MT‐TFL to extract the voxel‐intensity along the rostro‐caudal length. Linear mixed effects models examined age differences in LC intensity along this axis (age by z‐coordinate) as well as the modulation of sex (age by sex by z‐coordinate), implementing a random slope for position and random intercept for each subject. Result We found an age‐related quadratic gradient of the voxel intensity, in which lower voxels intensities were observed in the central section, not rostral or caudal section, in older individuals (Figure 1B; df1480, t=2.91,p= 0.0036). This gradient is sex dependent and shows that this effect is driven by lower intensities in older males compared to females in the central LC (df 1476, t=2.20, p=0.0274, Figure 1C). Conclusion We demonstrated a male vulnerability for lower medial LC structural properties. The medial LC is one of the regions initially affected by tau. Other studies reported a female vulnerability to tau. Further analyses including hormonal and biomarker data will help to elucidate the biological underpinnings of the sex‐differences in Alzheimer’s disease processes.
Materialart:
Online-Ressource
ISSN:
1552-5260
,
1552-5279
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2020
ZDB Id:
2201940-6
Permalink