Sistema de Salut de Catalunya
Institut Català de la Salut
[Sánchez-Benavides G, Grau-Rivera O] Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain. Hospital del Mar Research Institute, Barcelona, Spain. Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain. [Iranzo A] Sleep Disorders Center, Neurology Service, Hospital Clínic Universitari de Barcelona, University of Barcelona, Barcelona, Spain. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas, Madrid, Spain. [Giraldo DM, Buongiorno M] Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Malalties Neurovasculars, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-07-01T11:23:07Z
2025-07-01T11:23:07Z
2025-03
Alzheimer’s disease; Glymphatic system; Olfactory dysfunction
Enfermedad de Alzheimer; Sistema glinfático; Disfunción olfativa
Malaltia d'Alzheimer; Sistema glimfàtic; Disfunció olfactiva
An abnormal accumulation of misfolded proteins is a common feature shared by most neurodegenerative disorders. Olfactory dysfunction (OD) is common in the elderly population and is present in 90% of patients with Alzheimer's or Parkinson's disease, usually preceding the cognitive and motor symptoms onset by several years. Early Aβ, tau, and α-synuclein protein aggregates deposit in brain structures involved in odor processing (olfactory bulb and tract, piriform cortex, amygdala, entorhinal cortex, and hippocampus) and seem to underly OD. The glymphatic system is a glial-associated fluid transport system that facilitates the movement of brain fluids and removes brain waste during specific sleep stages. Notably, the glymphatic system became less functional in aging and it is impaired in several conditions, including neurodegenerative diseases. As the nasal pathway has been recently described as the main outflow exit of cerebrospinal fluid and solutes, we hypothesized that OD may indeed be a clinical marker of early glymphatic dysfunction through abnormal accumulation of pathological proteins in olfactory structures. This effect may be more pronounced in peri- and postmenopausal women due to the well-documented impact of estrogen loss on the locus coeruleus, which may disrupt multiple mechanisms involved in glymphatic clearance. If this hypothesis is confirmed, olfactory dysfunction might be considered as a clinical proxy of glymphatic failure in neurodegenerative diseases.
Gonzalo Sánchez-Benavides is supported by the Instituto de Salud Carlos III (ISCIII) through the project CP23/00039 (Miguel Servet contract).
Article
Published version
English
Sistema nerviós - Degeneració; Trastorns olfactius; Alzheimer, Malaltia d'; DISEASES::Nervous System Diseases::Neurodegenerative Diseases; DISEASES::Nervous System Diseases::Neurologic Manifestations::Sensation Disorders::Olfaction Disorders; DISEASES::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Dementia::Alzheimer Disease; ANATOMY::Nervous System::Central Nervous System::Brain::Glymphatic System; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades neurodegenerativas; ENFERMEDADES::enfermedades del sistema nervioso::manifestaciones neurológicas::trastornos sensoriales::trastornos del olfato; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::demencia::enfermedad de Alzheimer; ANATOMÍA::sistema nervioso::sistema nervioso central::encéfalo::sistema glinfático
MDPI
Diagnostics;15(6)
https://doi.org/10.3390/diagnostics15060719
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - VHIR [1655]
