Journal Article Ppublish 5 citations
PubMed: 39051173 DOI: 10.1002/alz.14131
Locus coeruleus integrity and neuropsychiatric symptoms in a cohort of early- and late-onset Alzheimer's disease.
Alzheimers Dement 20(9):6351-6364
Authors: Neus Falgàs, Marta Peña-González, Andrea Val-Guardiola, Agnès Pérez-Millan, Núria Guillén, Jordi Sarto, Diana Esteller, Beatriz Bosch, Guadalupe Fernández-Villullas, Adrià Tort-Merino, Gerard Mayà, Josep Maria Augé, Alex Iranzo, Mircea Balasa, Albert Lladó, Manuel Morales-Ruiz, Núria Bargalló, Emma Muñoz-Moreno, Lea T Grinberg, Raquel Sánchez-Valle
Affiliations
- 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.
- Magnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
- Neurology Service, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, Universitat de Barcelona, Barcelona, Spain.
- Biochemistry and Molecular Genetics Department-CDB, Hospital Clinic, IDIBAPS, CIBERehd, Barcelona, Spain.
- 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.
Abstract
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.
MeSH
Locus Coeruleus, Dementia, Norepinephrine, Alzheimer Disease, Biomarkers, Signs And Symptoms
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- Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus. bioRxiv, 2023
- Decreased practice effects in cognitively unimpaired amyloid betapositive individuals: a multicenter, longitudinal, cohort study. Alzheimers Dement, 2025
- Locus coeruleus integrity and neuropsychiatric symptoms in a cohort of early- and late-onset Alzheimer's disease. Alzheimers Dement, 2024
- Pupil-linked arousal, cortical activity, and cognition in Alzheimer's disease. Brain Commun, 2025