Brainstem volume is negatively associated with amyloid deposition in the Framingham Heart Study. (1st February 2022)

• Record Type: Journal Article
• Authors: Jacobs, Heidi I.L.; O'Donnell, Adrienne; Satizabal, Claudia L.; Hanseeuw, Bernard; Thibault, Emma G.; Koijs, Daniel; Sanchez, Justin S.; Buckley, Rachel F.; Yang, Qiong; Sperling, Reisa A.; Johnson, Keith A.; Beiser, Alexa S.; Seshadri, Sudha
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-01
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.055851
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The brainstem consists of various nuclei that accumulate tau early in the Alzheimer's disease (AD) trajectory. Previous studies discovered the genetic loci linked to brainstem volume, revealing genetic overlap with several neurological disorders, including AD. We aimed to investigate whether the volume of distinct parts of the brainstem are related to AD pathology, amyloid or tau, and whether this effect is modified by APOE genotype. Finally, we evaluated whether genetic variants related to total brainstem volumes are related to AD‐pathology by aggregating previously reported genetic loci into a brainstem polygenic risk score. Method: We included 267 individuals from the Framingham Heart Study who underwent 3T MRI, Flortaucipir (n=238) and PiB‐PET imaging on Siemens HR+ or GE‐Discovery GE PET cameras(mean age: 54 (SD:8) years, 51% male; 24% APOE‐E4; Figure 1). Subregional brainstem volumes were quantified using FreeSurfer 6.0 and adjusted for total cranial volume. Regional FTP‐PET, neocortical PiB‐PET signal were referenced to cerebellar grey and partial volume corrected (PVC). We performed several hierarchical regressions: 1) to associate each brainstem volume to neocortical PiB and tau in temporal lobe regions 2) to examine interactions between PiB and brainstem volumes on tau and 3) interactions between APOE and brainstem volume on tau. We then examined whether the brainstem polygenic risk score was associated with AD‐pathology. Covariates included age, sex and PET‐camera. Result: In both the PVC and non‐PVC analyses, lower medulla and pons volumes were consistently associated with greater neocortical PiB binding (Figure 2). Midbrain volume was at trend‐level negatively associated with inferior temporal and amygdala tau. No other associations were observed with tau. We observed no interactions between brainstem volumes and PiB or APOE on regional tau. The brainstem polygenic risk score was not associated with AD‐pathology (Figure 3). Conclusion: Lower brainstem volume, in particular medulla and pons, is associated with amyloid deposition in a cohort of middle‐aged individuals. There is no evidence for associations with known brainstem loci, suggesting that these associations may occur via different or indirect pathways, or that lower brainstem volumes may be a reflection of overall disease progression and neurodegeneration.