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

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• dc.contributor.author Falgas, Neus
• dc.contributor.author Peña-González, Marta
• dc.contributor.author Guillén, Núria
• dc.contributor.author Morales-Ruiz, Manuel
• dc.contributor.author Sánchez Valle, Raquel
• dc.date.accessioned 2025-11-24T07:03:45Z
• dc.date.available 2025-11-24T07:03:45Z
• dc.date.issued 2024
• dc.description.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.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Falgàs N, Peña-González M, Val-Guardiola A, Pérez-Millan A, Guillén N, Sarto J, et al. Locus coeruleus integrity and neuropsychiatric symptoms in a cohort of early- and late-onset Alzheimer’s disease. Alzheimers Dement. 2024;20(9):6351–64. DOI: 10.1002/alz.14131
• dc.identifier.doi http://dx.doi.org/10.1002/alz.14131
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/71973
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimer's & Dementia. 2024;20(9):6351–64
• dc.rights © 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Alzheimer's diseaseen
• dc.subject.keyword Early-onset Alzheimer's diseaseen
• dc.subject.keyword Locus coeruleusen
• dc.subject.keyword Neuromodulatory subcortical systemsen
• dc.subject.keyword Neuropsychiatric symptomsen
• dc.subject.keyword Selective vulnerabilityen
• dc.title Locus coeruleus integrity and neuropsychiatric symptoms in a cohort of early- and late-onset Alzheimer's diseaseen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion