Locus coeruleus integrity and neuropsychiatric symptoms in a cohort of early- and late-onset Alzheimer's disease.

Autor: Falgàs N; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.; Global Brain Health Institute, University of California, San Francisco, California, USA., Peña-González M; Magnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain., Val-Guardiola A; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Pérez-Millan A; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Guillén N; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Sarto J; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Esteller D; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Bosch B; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Fernández-Villullas G; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Tort-Merino A; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Mayà G; Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Universitat de Barcelona, Barcelona, Spain., Augé JM; Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain., Iranzo A; Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Universitat de Barcelona, Barcelona, Spain., Balasa M; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Lladó A; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain., Morales-Ruiz M; Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain., Bargalló N; Magnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain., Muñoz-Moreno E; Magnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain., Grinberg LT; Global Brain Health Institute, University of California, San Francisco, California, USA.; Department of Neurology, Memory & Aging Center, Weill Institute for Neurosciences, University of California, San Francisco, California, USA.; Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil., Sánchez-Valle R; Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Barcelona, Catalonia, Spain.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Sep; Vol. 20 (9), pp. 6351-6364. Date of Electronic Publication: 2024 Jul 25.
DOI: 10.1002/alz.14131
Abstrakt: Introduction: Early-onset Alzheimer's disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late-onset Alzheimer's disease (LOAD). We aim to determine the differences in the severity of neuropsychiatric symptoms and locus coeruleus (LC) integrity between EOAD and LOAD accounting for disease stage.
Methods: One hundred four subjects with AD diagnosis and 32 healthy controls were included. Participants underwent magnetic resonance imaging (MRI) to measure LC integrity, measures of noradrenaline levels in cerebrospinal fluid (CSF) and Neuropsychiatric Inventory (NPI). We analyzed LC-noradrenaline measurements and clinical and Alzheimer's disease (AD) biomarker associations.
Results: EOAD showed higher NPI scores, lower LC integrity, and similar levels of CSF noradrenaline compared to LOAD. Notably, EOAD exhibited lower LC integrity independently of disease stage. LC integrity negatively correlated with neuropsychiatric symptoms. Noradrenaline levels were increased in AD correlating with AD biomarkers.
Discussion: Decreased LC integrity negatively contributes to neuropsychiatric symptoms. The higher LC degeneration in EOAD compared to LOAD could explain the more severe neuropsychiatric symptoms in EOAD.
Highlights: LC degeneration is greater in early-onset AD (EOAD) compared to late-onset AD. Tau-derived LC degeneration drives a higher severity of neuropsychiatric symptoms. EOAD harbors a more profound selective vulnerability of the LC system. LC degeneration is associated with an increase of cerebrospinal fluid noradrenaline levels in AD.
(© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE