@article{37c13960cf4a499aa13760b8dfddde59,
title = "Waning locus coeruleus integrity precedes cortical tau accrual in preclinical autosomal dominant Alzheimer's disease",
abstract = "Introduction Autopsy studies recognize the locus coeruleus (LC) as one of the first sites accumulating tau in Alzheimer's disease (AD). Recent AD work related in vivo LC magnetic resonance imaging (MRI) integrity to tau and cognitive decline; however, relationships of LC integrity to age, tau, and cognition in autosomal dominant AD (ADAD) remain unexplored. Methods We associated LC integrity (3T-MRI) with estimated years of onset, cortical amyloid beta, regional tau (positron emission tomography [PET]) and memory (Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word-List-Learning) among 27 carriers and 27 non-carriers of the presenilin-1 (PSEN1) E280A mutation. Longitudinal changes between LC integrity and tau were evaluated in 10 carriers. Results LC integrity started to decline at age 32 in carriers, 12 years before clinical onset, and 20 years earlier than in sporadic AD. LC integrity was negatively associated with cortical tau, independent of amyloid beta, and predicted precuneus tau increases. LC integrity was positively associated with memory. Discussion These findings support LC integrity as marker of disease progression in preclinical ADAD.",
keywords = "Alzheimer's disease, autosomal dominant, brainstem, early onset, locus coeruleus, tau, SURFACE-BASED ANALYSIS, COGNITIVE DECLINE, BIOMARKER, BRAIN, PRESENILIN-1, MODULATION, DEPOSITION",
author = "H.I.L. Jacobs and J.A. Becker and K. Kwong and D. Munera and L. Ramirez-Gomez and N. Engels-Dominguez and J.S. Sanchez and C. Vila-Castelar and A. Baena and R.A. Sperling and K.A. Johnson and F. Lopera and Y.T. Quiroz",
note = "Funding Information: The authors thank the Colombian families for contributing their valuable time and effort, without which this study would not have been possible. The authors thank the research staff of the Group of Neuroscience of Antioquia for their help coordinating study visits for the COLBOS project. Dr Quiroz was supported by grants from the National Institutes of Health (NIH) Office of the Director (DP5OD019833), National Institute on Aging (NIA; R01AG054671), the Alzheimer's Association, and Massachusetts General Hospital ECOR. Dr. Lopera was supported by NIA, API Colombia, and an Anonymous Foundation. Dr Jacobs receives funding from the NIH‐NIA R01AG062559, R01AG068062, and R21AG074220. Dr Sperling receives research support for NIH grants P01AG036694, P50AG005134, 2009‐2020, and U19AG10483, as well as from Eli Lilly (clinical trial) and the Alzheimer's Association. Dr Johnson has received support from a joint NIH‐Lilly‐sponsored clinical trial (A4 Study – U19AG10483) and received research support from NIH grants R01AG027435, P50AG00513421, P01AG036694, R01AG046396, and U01AG024904, as well as the Alzheimer's Association and Marr Foundation. Dr Vila‐Castelar receives funding from the Alzheimer's Association (2019‐AARF‐644631). PSEN1 Funding Information: The authors thank the PSEN1 Colombian families for contributing their valuable time and effort, without which this study would not have been possible. The authors thank the research staff of the Group of Neuroscience of Antioquia for their help coordinating study visits for the COLBOS project. Dr Quiroz was supported by grants from the National Institutes of Health (NIH) Office of the Director (DP5OD019833), National Institute on Aging (NIA; R01AG054671), the Alzheimer's Association, and Massachusetts General Hospital ECOR. Dr. Lopera was supported by NIA, API Colombia, and an Anonymous Foundation. Dr Jacobs receives funding from the NIH-NIA R01AG062559, R01AG068062, and R21AG074220. Dr Sperling receives research support for NIH grants P01AG036694, P50AG005134, 2009-2020, and U19AG10483, as well as from Eli Lilly (clinical trial) and the Alzheimer's Association. Dr Johnson has received support from a joint NIH-Lilly-sponsored clinical trial (A4 Study – U19AG10483) and received research support from NIH grants R01AG027435, P50AG00513421, P01AG036694, R01AG046396, and U01AG024904, as well as the Alzheimer's Association and Marr Foundation. Dr Vila-Castelar receives funding from the Alzheimer's Association (2019-AARF-644631). Publisher Copyright: {\textcopyright} 2022 the Alzheimer's Association.",
year = "2023",
month = jan,
doi = "10.1002/alz.12656",
language = "English",
volume = "19",
pages = "169--180",
journal = "Alzheimer's & Dementia",
issn = "1552-5260",
publisher = "John Wiley & Sons Inc.",
number = "1",
}