biostudies-literatureJacobs HILNIA NIH HHSNational Institutes of HealthAlzheimer&apos;s AssociationNational Institute on AgingNIH HHS169-180https://www.ebi.ac.uk/biostudies/studies/S-EPMC9481982biostudies-literatureUnknown19(1)<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>These findings support LC integrity as marker of disease progression in preclinical ADAD.Alzheimer's & dementia : the journal of the Alzheimer's AssociationWaning locus coeruleus integrity precedes cortical tau accrual in preclinical autosomal dominant Alzheimer's disease.PMC9481982P50AG005134R01 AG054671P50 AG005134R01 AG062559R21 AG074220DP5OD019833P30 AG062421R01AG054671DP5 OD019833U19AG10483P01 AG036694R01 AG068062U19 AG010483R01AG068062U01AG024904R01AG0463962019‐AARF‐644631R01AG027435P01AG036694R01AG062559U01 AG024904R01 AG027435R21AG074220R01 AG046396Becker JAEngels-Dominguez NSanchez JSVila-Castelar CJacobs HILKwong KJohnson KASperling RAQuiroz YTRamirez-Gomez LLopera FBaena AMunera DfalseWaning locus coeruleus integrity precedes cortical tau accrual in preclinical autosomal dominant Alzheimer's disease.<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>These findings support LC integrity as marker of disease progression in preclinical ADAD.2023-01-01T00:00:00Z2023 Jan2025-04-04T07:44:53.38Z2025-04-04T07:44:53.38ZS-EPMC94819823529808310.1002/alz.12656