Heidi I L Jacobs1,2, John Alex Becker1, Kenneth Kwong3, Diana Munera4, Liliana Ramirez-Gomez5, Nina Engels-Domínguez1,2, Justin S Sanchez1, Clara Vila-Castelar4, Ana Baena6, Reisa A Sperling3,5,7, Keith A Johnson1,7, Francisco Lopera6, Yakeel T Quiroz4,5,6. 1. Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA. 2. Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, The Netherlands. 3. Athinoula A. Martinos Center for Biomedial Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA. 4. Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA. 5. Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA. 6. Grupo Neurociencias de Antioquia, Universidad de Antioquia, Medellín, Colombia. 7. Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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.
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.
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Authors: Justin S Sanchez; J Alex Becker; Heidi I L Jacobs; Bernard J Hanseeuw; Shu Jiang; Aaron P Schultz; Michael J Properzi; Samantha R Katz; Alexa Beiser; Claudia L Satizabal; Adrienne O'Donnell; Charles DeCarli; Ron Killiany; Georges El Fakhri; Marc D Normandin; Teresa Gómez-Isla; Yakeel T Quiroz; Dorene M Rentz; Reisa A Sperling; Sudha Seshadri; Jean Augustinack; Julie C Price; Keith A Johnson Journal: Sci Transl Med Date: 2021-01-20 Impact factor: 17.956
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