{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:09:54Z","timestamp":1792674594438,"version":"4.5.0"},"reference-count":86,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII)","award":["CP23\/00039"],"award-info":[{"award-number":["CP23\/00039"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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\u2019s or Parkinson\u2019s disease, usually preceding the cognitive and motor symptoms onset by several years. Early A\u03b2, tau, and \u03b1-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.<\/jats:p>","DOI":"10.3390\/diagnostics15060719","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T10:16:45Z","timestamp":1741861005000},"page":"719","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Olfactory Dysfunction as a Clinical Marker of Early Glymphatic Failure in Neurodegenerative Diseases"],"prefix":"10.3390","volume":"15","author":[{"given":"Gonzalo","family":"S\u00e1nchez-Benavides","sequence":"first","affiliation":[{"name":"Barcelona\u03b2eta Brain Research Center (BBRC), Pasqual Maragall Foundation, 08005 Barcelona, Spain"},{"name":"Hospital del Mar Research Institute, 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Iranzo","sequence":"additional","affiliation":[{"name":"Sleep Disorders Center, Neurology Service, Hospital Cl\u00ednic Universitari de Barcelona, University of Barcelona, 08036 Barcelona, Spain"},{"name":"Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-5341","authenticated-orcid":false,"given":"Oriol","family":"Grau-Rivera","sequence":"additional","affiliation":[{"name":"Barcelona\u03b2eta Brain Research Center (BBRC), Pasqual Maragall Foundation, 08005 Barcelona, Spain"},{"name":"Hospital del Mar Research Institute, 08003 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8821-7662","authenticated-orcid":false,"given":"Darly Milena","family":"Giraldo","sequence":"additional","affiliation":[{"name":"Neurology Department, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Neurovascular Diseases Research Group, Vall d\u2019Hebron Research Institute, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariateresa","family":"Buongiorno","sequence":"additional","affiliation":[{"name":"Neurology Department, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Neurovascular Diseases Research Group, Vall d\u2019Hebron Research Institute, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","article-title":"A Paravascular Pathway Facilitates CSF Flow through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid \u03b2","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. 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