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

被引：62

作者：

Dahl, Martin J. ^{[1
,2
]}

Mather, Mara ^{[2
]}

Werkle-Bergner, Markus ^{[1
]}

Kennedy, Briana L. ^{[2
,3
]}

Guzman, Samuel ^{[4
]}

Hurth, Kyle ^{[4
]}

Miller, Carol A. ^{[4
]}

Qiao, Yuchuan ^{[5
]}

Shi, Yonggang ^{[5
]}

Chui, Helena C. ^{[6
]}

Ringman, John M. ^{[6
]}

机构：

[1] Max Planck Inst Human Dev, Ctr Lifespan Psychol, D-14195 Berlin, Germany

[2] Univ Southern Calif, Davis Sch Gerontol, Los Angeles, CA 90007 USA

[3] Univ Western Australia, Sch Psychol Sci, Perth, WA, Australia

[4] Univ Southern Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90007 USA

[5] Univ Southern Calif, Keck Sch Med, USC Stevens Neuroimaging & Informat Inst, Lab Neuro Imaging LONI, Los Angeles, CA 90007 USA

[6] Univ Southern Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90007 USA

来源：

NEUROBIOLOGY OF AGING | 2022年 / 112卷

关键词：

Locus coeruleus; Autosomal-dominant Alzheimer's disease; Noradrenaline; Norepinephrine; Tau pathology; Neurodegeneration; A431E; MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; IN-VIVO VISUALIZATION; VERBAL-LEARNING TEST; NORADRENALINE SYSTEM; IMAGE SEGMENTATION; MRI CONTRAST; HUMAN BRAIN; AGE; MUTATION;

D O I：

10.1016/j.neurobiolaging.2021.11.006

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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. (C) 2021 The Authors. Published by Elsevier Inc.

引用

页码：39 / 54

页数：16

共 116 条

[81] Homozygosity for the A431E mutation in PSEN1 presenting with a relatively aggressive phenotype [J].