Abnormally phosphorylated tau, an indicator of Alzheimer’s disease, accumulates in the first decades of life in the locus coeruleus (LC), the brain’s main noradrenaline supply. However, technical challenges in in-vivo assessments have impeded research into the role of the LC in Alzheimer’s disease.
We studied participants with or known to be at-risk for mutations in genes causing autosomal-dominant Alzheimer’s disease (ADAD) with early onset, providing a unique window into the pathogenesis of Alzheimer’s largely disentangled from age-related factors. Using high-resolution MRI and tau PET, we found lower rostral LC integrity in symptomatic participants. LC integrity was associated with individual differences in tau burden and memory decline. Post-mortem analyses in a separate set of carriers of the same mutation confirmed substantial neuronal loss in the LC.
Our findings link LC degeneration to tau burden and memory in Alzheimer’s, and highlight a role of the noradrenergic system in this neurodegenerative disease.
Dahl, M. J., Mather, M., Werkle-Bergner, M., Kennedy, B. L., Guzman, S., Hurth, K., Miller, C. A., Qiao, Y.,Shi, Y., Chui, H. C., & Ringman, J. M. (2022). Locus coeruleus integrity is related to tau burden and memory loss in autosomal-dominant Alzheimer’s disease. Neurobiology of Aging, 112, 39–54. Article Link