Locus coeruleus integrity is related to tau burden and memory loss in autosomal-dominant Alzheimer's disease.

Martin J Dahl, Mara Mather, Markus Werkle-Bergner, Briana L Kennedy, Samuel Guzman, Kyle Hurth, Carol A Miller, Yuchuan Qiao, Yonggang Shi, Helena C Chui, John M Ringman

Neurobiology of aging 2022 Apr

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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. Copyright © 2021. Published by Elsevier Inc.

Citation

Martin J Dahl, Mara Mather, Markus Werkle-Bergner, Briana L Kennedy, Samuel Guzman, Kyle Hurth, Carol A Miller, Yuchuan Qiao, Yonggang Shi, Helena C Chui, John M Ringman. Locus coeruleus integrity is related to tau burden and memory loss in autosomal-dominant Alzheimer's disease. Neurobiology of aging. 2022 Apr;112:39-54