{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:35:45Z","timestamp":1789385745707,"version":"build-2803163510"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"UCLouvain Action de Recherche Concert\u00e9e"},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek Vlaanderen","doi-asserted-by":"crossref","award":["1225725N"],"award-info":[{"award-number":["1225725N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek Vlaanderen","doi-asserted-by":"crossref","award":["G065721N"],"award-info":[{"award-number":["G065721N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007355","name":"Fondation Louvain","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007355","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SAO-FRA Alzheimer Research Foundation","award":["SAO-FRA 2018\/0025"],"award-info":[{"award-number":["SAO-FRA 2018\/0025"]}]},{"DOI":"10.13039\/501100022601","name":"Queen Elisabeth Medical Foundation","doi-asserted-by":"crossref","award":["FMRE AlzHEX"],"award-info":[{"award-number":["FMRE AlzHEX"]}],"id":[{"id":"10.13039\/501100022601","id-type":"DOI","asserted-by":"crossref"}]},{"name":"F.R.S.-FNRS","award":["FNRS J.0106.22"],"award-info":[{"award-number":["FNRS J.0106.22"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"DOI":"10.1007\/s00401-025-02902-6","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T08:57:33Z","timestamp":1750323453000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The olfactory epithelium: a critical gateway for pathological tau propagation and a target for mitigating tauopathy in the central nervous system"],"prefix":"10.1007","volume":"149","author":[{"given":"Marion","family":"Dourte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Pa\u00eetre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mongia","family":"Bouchoucha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilien","family":"Boyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra O.","family":"Tom\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Doeraene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Huart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karelle","family":"Leroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar Rudolf","family":"Thal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabelle","family":"Decottignies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Hanseeuw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Suelves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Kienlen-Campard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"2902_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189727","author":"F Ahmad","year":"2021","unstructured":"Ahmad F, Mein H, Jing Y, Zhang H, Liu P (2021) Behavioural functions and cerebral blood flow in a P301S Tauopathy mouse model: a time-course study. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms22189727","journal-title":"Int J Mol Sci"},{"key":"2902_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155431","author":"A Ahnaou","year":"2020","unstructured":"Ahnaou A, Rodriguez-Manrique D, Biermans R, Embrechts S, Manyakov NV, Drinkenburg WH (2020) Functional alterations in the olfactory neuronal circuit occur before hippocampal plasticity deficits in the P301S mouse model of tauopathy: implications for early diagnosis and translational research in Alzheimer\u2019s disease. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms21155431","journal-title":"Int J Mol Sci"},{"issue":"10","key":"2902_CR3","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1523\/jneurosci.2376-20.2021","volume":"41","author":"M Amani","year":"2021","unstructured":"Amani M, Lauterborn JC, Le AA, Cox BM, Wang W, Quintanilla J et al (2021) Rapid aging in the Perforant path projections to the rodent dentate gyrus. J Neurosci 41(10):2301\u20132312. https:\/\/doi.org\/10.1523\/jneurosci.2376-20.2021","journal-title":"J Neurosci"},{"issue":"2","key":"2902_CR4","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s00401-020-02251-6","volume":"141","author":"L Arag\u00e3o Gomes","year":"2021","unstructured":"Arag\u00e3o Gomes L, Uytterhoeven V, Lopez-Sanmartin D, Tom\u00e9 SO, Tousseyn T, Vandenberghe R et al (2021) Maturation of neuronal AD-tau pathology involves site-specific phosphorylation of cytoplasmic and synaptic tau preceding conformational change and fibril formation. Acta Neuropathol 141(2):173\u2013192. https:\/\/doi.org\/10.1007\/s00401-020-02251-6","journal-title":"Acta Neuropathol"},{"key":"2902_CR5","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1111\/j.1749-6632.1998.tb10656.x","volume":"855","author":"SE Arnold","year":"1998","unstructured":"Arnold SE, Smutzer GS, Trojanowski JQ, Moberg PJ (1998) Cellular and molecular neuropathology of the olfactory epithelium and central olfactory pathways in Alzheimer\u2019s disease and schizophrenia. Ann N Y Acad Sci 855:762\u2013775. https:\/\/doi.org\/10.1111\/j.1749-6632.1998.tb10656.x","journal-title":"Ann N Y Acad Sci"},{"issue":"6","key":"2902_CR6","first-page":"265","volume":"25","author":"J Attems","year":"2006","unstructured":"Attems J, Jellinger KA (2006) Olfactory tau pathology in Alzheimer disease and mild cognitive impairment. Clin Neuropathol 25(6):265\u2013271","journal-title":"Clin Neuropathol"},{"issue":"2","key":"2902_CR7","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3233\/jad-2005-7208","volume":"7","author":"J Attems","year":"2005","unstructured":"Attems J, Lintner F, Jellinger KA (2005) Olfactory involvement in aging and Alzheimer\u2019s disease: an autopsy study. J Alzheimers Dis 7(2):149\u2013157. https:\/\/doi.org\/10.3233\/jad-2005-7208","journal-title":"J Alzheimers Dis"},{"key":"2902_CR8","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s00401-014-1261-7","volume":"127","author":"J Attems","year":"2014","unstructured":"Attems J, Walker L, Jellinger KA (2014) Olfactory bulb involvement in neurodegenerative diseases. Acta Neuropathol 127:459\u2013475. https:\/\/doi.org\/10.1007\/s00401-014-1261-7","journal-title":"Acta Neuropathol"},{"key":"2902_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2014.00063","author":"AW Barrios","year":"2014","unstructured":"Barrios AW, N\u00fa\u00f1ez G, S\u00e1nchez QP, Salazar I (2014) Anatomy, histochemistry, and immunohistochemistry of the olfactory subsystems in mice. Front Neuroanat. https:\/\/doi.org\/10.3389\/fnana.2014.00063","journal-title":"Front Neuroanat"},{"key":"2902_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100956","volume":"55","author":"P Bathini","year":"2019","unstructured":"Bathini P, Brai E, Auber LA (2019) Olfactory dysfunction in the pathophysiological continuum of dementia. Ageing Res Rev 55:100956. https:\/\/doi.org\/10.1016\/j.arr.2019.100956","journal-title":"Ageing Res Rev"},{"issue":"4","key":"2902_CR11","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","volume":"112","author":"H Braak","year":"2006","unstructured":"Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 112(4):389\u2013404. https:\/\/doi.org\/10.1007\/s00401-006-0127-z","journal-title":"Acta Neuropathol"},{"issue":"4","key":"2902_CR12","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"H Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82(4):239\u2013259. https:\/\/doi.org\/10.1007\/BF00308809","journal-title":"Acta Neuropathol"},{"issue":"33","key":"2902_CR13","doi-asserted-by":"publisher","first-page":"13449","DOI":"10.1523\/jneurosci.1387-13.2013","volume":"33","author":"J Chapuis","year":"2013","unstructured":"Chapuis J, Cohen Y, He X, Zhang Z, Jin S, Xu F et al (2013) Lateral entorhinal modulation of piriform cortical activity and fine odor discrimination. J Neurosci 33(33):13449\u201313459. https:\/\/doi.org\/10.1523\/jneurosci.1387-13.2013","journal-title":"J Neurosci"},{"issue":"5","key":"2902_CR14","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1055\/s-0033-1361837","volume":"75","author":"CR Chen","year":"2014","unstructured":"Chen CR, Kachramanoglou C, Li D, Andrews P, Choi D (2014) Anatomy and cellular constituents of the human olfactory mucosa: a review. J Neurol Surg B Skull Base 75(5):293\u2013300. https:\/\/doi.org\/10.1055\/s-0033-1361837","journal-title":"J Neurol Surg B Skull Base"},{"issue":"7","key":"2902_CR15","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/ncb1901","volume":"11","author":"F Clavaguera","year":"2009","unstructured":"Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A et al (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 11(7):909\u2013913. https:\/\/doi.org\/10.1038\/ncb1901","journal-title":"Nat Cell Biol"},{"key":"2902_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101416","volume":"70","author":"X Dan","year":"2021","unstructured":"Dan X, Wechter N, Gray S, Mohanty JG, Croteau DL, Bohr VA (2021) Olfactory dysfunction in aging and neurodegenerative diseases. Ageing Res Rev 70:101416. https:\/\/doi.org\/10.1016\/j.arr.2021.101416","journal-title":"Ageing Res Rev"},{"issue":"1","key":"2902_CR17","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","volume":"14","author":"MA DeTure","year":"2019","unstructured":"DeTure MA, Dickson DW (2019) The neuropathological diagnosis of Alzheimer\u2019s disease. Mol Neurodegener 14(1):32. https:\/\/doi.org\/10.1186\/s13024-019-0333-5","journal-title":"Mol Neurodegener"},{"issue":"1","key":"2902_CR18","doi-asserted-by":"publisher","first-page":"4809","DOI":"10.1038\/s41467-024-48462-3","volume":"15","author":"I Diez","year":"2024","unstructured":"Diez I, Ortiz-Ter\u00e1n L, Ng TSC, Albers MW, Marshall G et al (2024) Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging. Nat Commun 15(1):4809. https:\/\/doi.org\/10.1038\/s41467-024-48462-3","journal-title":"Nat Commun"},{"issue":"6","key":"2902_CR19","doi-asserted-by":"publisher","first-page":"709","DOI":"10.4155\/tde.14.41","volume":"5","author":"PG Djupesland","year":"2014","unstructured":"Djupesland PG, Messina JC, Mahmoud RA (2014) The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview. Ther Deliv 5(6):709\u2013733. https:\/\/doi.org\/10.4155\/tde.14.41","journal-title":"Ther Deliv"},{"key":"2902_CR20","doi-asserted-by":"crossref","unstructured":"Dorman DC (2010) 13.15\u2014Olfactory system. In: McQueen CA (ed) Comprehensive toxicology (Second Edition). Elsevier, Oxford, pp 263\u2013276","DOI":"10.1016\/B978-0-08-046884-6.01316-6"},{"issue":"6","key":"2902_CR21","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/S1474-4422(17)30123-0","volume":"16","author":"RL Doty","year":"2017","unstructured":"Doty RL (2017) Olfactory dysfunction in neurodegenerative diseases: is there a common pathological substrate? Lancet Neurol 16(6):478\u2013488. https:\/\/doi.org\/10.1016\/S1474-4422(17)30123-0","journal-title":"Lancet Neurol"},{"key":"2902_CR22","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/978-981-32-9358-8_23","volume":"1184","author":"S Dujardin","year":"2019","unstructured":"Dujardin S, Hyman BT (2019) Tau prion-like propagation: state of the art and current challenges. Adv Exp Med Biol 1184:305\u2013325. https:\/\/doi.org\/10.1007\/978-981-32-9358-8_23","journal-title":"Adv Exp Med Biol"},{"key":"2902_CR23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032117","author":"I Fatuzzo","year":"2023","unstructured":"Fatuzzo I, Niccolini GF, Zoccali F, Cavalcanti L, Bellizzi MG, Riccardi G et al (2023) Neurons, nose, and neurodegenerative diseases: olfactory function and cognitive impairment. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms24032117","journal-title":"Int J Mol Sci"},{"key":"2902_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/cells13070615","author":"R Franco","year":"2024","unstructured":"Franco R, Garrig\u00f3s C, Lillo J (2024) The olfactory trail of neurodegenerative diseases. Cells. https:\/\/doi.org\/10.3390\/cells13070615","journal-title":"Cells"},{"issue":"1","key":"2902_CR25","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s00401-008-0383-1","volume":"116","author":"H Fujishiro","year":"2008","unstructured":"Fujishiro H, Tsuboi Y, Lin WL, Uchikado H, Dickson DW (2008) Co-localization of tau and alpha-synuclein in the olfactory bulb in Alzheimer\u2019s disease with amygdala Lewy bodies. Acta Neuropathol 116(1):17\u201324. https:\/\/doi.org\/10.1007\/s00401-008-0383-1","journal-title":"Acta Neuropathol"},{"issue":"754","key":"2902_CR26","doi-asserted-by":"publisher","first-page":"eadj5958","DOI":"10.1126\/scitranslmed.adj5958","volume":"16","author":"S Gaikwad","year":"2024","unstructured":"Gaikwad S, Puangmalai N, Sonawane M, Montalbano M, Price R, Iyer MS et al (2024) Nasal tau immunotherapy clears intracellular tau pathology and improves cognitive functions in aged tauopathy mice. Sci Transl Med 16(754):eadj5958. https:\/\/doi.org\/10.1126\/scitranslmed.adj5958","journal-title":"Sci Transl Med"},{"issue":"1","key":"2902_CR27","first-page":"1","volume":"19","author":"F Gallyas","year":"1971","unstructured":"Gallyas F (1971) Silver staining of Alzheimer\u2019s neurofibrillary changes by means of physical development. Acta Morphol Acad Sci Hung 19(1):1\u20138","journal-title":"Acta Morphol Acad Sci Hung"},{"issue":"10","key":"2902_CR28","doi-asserted-by":"publisher","first-page":"175","DOI":"10.21037\/atm.2018.04.23","volume":"6","author":"YL Gao","year":"2018","unstructured":"Gao YL, Wang N, Sun FR, Cao XP, Zhang W, Yu JT (2018) Tau in neurodegenerative disease. Ann Transl Med 6(10):175","journal-title":"Ann Transl Med"},{"key":"2902_CR29","unstructured":"Gayatri D (2023) Handbook of clinical neurology. In: Chapter 12\u2014The tauopathies Vol 196"},{"issue":"1","key":"2902_CR30","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/S0021-9258(18)48531-6","volume":"267","author":"SG Greenberg","year":"1992","unstructured":"Greenberg SG, Davies P, Schein JD, Binder LI (1992) Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau. J Biol Chem 267(1):564\u2013569","journal-title":"J Biol Chem"},{"key":"2902_CR31","doi-asserted-by":"publisher","first-page":"123809","DOI":"10.1016\/j.ijpharm.2024.123809","volume":"652","author":"H Guo","year":"2024","unstructured":"Guo H, Wang G, Zhai Z, Huang J, Huang Z, Zhou Y et al (2024) Rivastigmine nasal spray for the treatment of Alzheimer\u2019s disease: olfactory deposition and brain delivery. Int J Pharmaceut 652:123809. https:\/\/doi.org\/10.1016\/j.ijpharm.2024.123809","journal-title":"Int J Pharmaceut"},{"issue":"2","key":"2902_CR32","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/0006-8993(78)90460-2","volume":"140","author":"JW Harding","year":"1978","unstructured":"Harding JW, Getchell TV, Margolis FL (1978) Denervation of the primary olfactory pathway in mice. V. Long-term effect of intranasal ZnSO4 irrigation on behavior, biochemistry and morphology. Brain Res 140(2):271\u2013285. https:\/\/doi.org\/10.1016\/0006-8993(78)90460-2","journal-title":"Brain Res"},{"key":"2902_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2021.637036","volume":"15","author":"L Hildebrandt-Einfeldt","year":"2021","unstructured":"Hildebrandt-Einfeldt L, Yap K, Paul MH, Stoffer C, Zahn N, Drakew A et al (2021) Crossed entorhino-dentate projections form and terminate with correct layer-specificity in organotypic slice cultures of the mouse hippocampus. Front Neuroanat 15:637036. https:\/\/doi.org\/10.3389\/fnana.2021.637036","journal-title":"Front Neuroanat"},{"issue":"4","key":"2902_CR34","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1093\/chemse\/bjj035","volume":"31","author":"M Keller","year":"2006","unstructured":"Keller M, Douhard Q, Baum MJ, Bakker J (2006) Destruction of the main olfactory epithelium reduces female sexual behavior and olfactory investigation in female mice. Chem Senses 31(4):315\u2013323. https:\/\/doi.org\/10.1093\/chemse\/bjj035","journal-title":"Chem Senses"},{"key":"2902_CR35","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3389\/fnagi.2020.00208","volume":"12","author":"K Kondo","year":"2020","unstructured":"Kondo K, Kikuta S, Ueha R, Suzukawa K, Yamasoba T (2020) Age-related olfactory dysfunction: epidemiology, pathophysiology, and clinical management. Front Aging Neurosci 12:208. https:\/\/doi.org\/10.3389\/fnagi.2020.00208","journal-title":"Front Aging Neurosci"},{"issue":"1","key":"2902_CR36","doi-asserted-by":"publisher","first-page":"34","DOI":"10.2478\/s13380-013-0108-3","volume":"4","author":"T Kov\u00e1cs","year":"2013","unstructured":"Kov\u00e1cs T (2013) The olfactory system in Alzheimer\u2019s disease: pathology, pathophysiology and pathway for therapy. Transl Neurosci 4(1):34\u201345. https:\/\/doi.org\/10.2478\/s13380-013-0108-3","journal-title":"Transl Neurosci"},{"issue":"2","key":"2902_CR37","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1097\/00001756-200102120-00021","volume":"12","author":"T Kov\u00e1cs","year":"2001","unstructured":"Kov\u00e1cs T, Cairns NJ, Lantos PL (2001) Olfactory centres in Alzheimer\u2019s disease: olfactory bulb is involved in early Braak\u2019s stages. NeuroReport 12(2):285\u2013288","journal-title":"NeuroReport"},{"issue":"2","key":"2902_CR38","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1177\/10738584221126090","volume":"30","author":"M Lad","year":"2024","unstructured":"Lad M, Sedley W, Griffiths TD (2024) Sensory loss and risk of dementia. Neuroscientist 30(2):247\u2013259. https:\/\/doi.org\/10.1177\/10738584221126090","journal-title":"Neuroscientist"},{"issue":"1","key":"2902_CR39","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1186\/s12974-022-02657-x","volume":"19","author":"BJ LaFever","year":"2022","unstructured":"LaFever BJ, Imamura F (2022) Effects of nasal inflammation on the olfactory bulb. J Neuroinflammation 19(1):294. https:\/\/doi.org\/10.1186\/s12974-022-02657-x","journal-title":"J Neuroinflammation"},{"key":"2902_CR40","doi-asserted-by":"crossref","unstructured":"Laska M (2017) Human and animal olfactory capabilities compared. pp 675\u2013689","DOI":"10.1007\/978-3-319-26932-0_32"},{"issue":"148","key":"2902_CR41","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.brainresbull.2019.03.006","volume":"1","author":"S Li","year":"2019","unstructured":"Li S, Li W, Wu X, Li J, Yang J, Tu C et al (2019) Olfactory deficit is associated with mitral cell dysfunction in the olfactory bulb of P301S tau transgenic mice. Brain Res Bull 1(148):34\u201345. https:\/\/doi.org\/10.1016\/j.brainresbull.2019.03.006","journal-title":"Brain Res Bull"},{"issue":"7","key":"2902_CR42","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s40263-022-00930-4","volume":"36","author":"A Lofts","year":"2022","unstructured":"Lofts A, Abu-Hijleh F, Rigg N, Mishra RK, Hoare T (2022) Using the intranasal route to administer drugs to treat neurological and psychiatric illnesses: rationale, successes, and future needs. CNS Drugs 36(7):739\u2013770. https:\/\/doi.org\/10.1007\/s40263-022-00930-4","journal-title":"CNS Drugs"},{"issue":"1","key":"2902_CR43","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1021\/cn1000843","volume":"2","author":"JN Lundstr\u00f6m","year":"2011","unstructured":"Lundstr\u00f6m JN, Boesveldt S, Albrecht J (2011) Central processing of the chemical senses: an overview. ACS Chem Neurosci 2(1):5\u201316. https:\/\/doi.org\/10.1021\/cn1000843","journal-title":"ACS Chem Neurosci"},{"issue":"2","key":"2902_CR44","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.neurobiolaging.2014.10.033","volume":"36","author":"G Martel","year":"2015","unstructured":"Martel G, Simon A, Nocera S, Kalainathan S, Pidoux L, Blum D et al (2015) Aging, but not tau pathology, impacts olfactory performances and somatostatin systems in THY-Tau22 mice. Neurobiol Aging 36(2):1013\u20131028. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2014.10.033","journal-title":"Neurobiol Aging"},{"issue":"1","key":"2902_CR45","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/aja.1001420106","volume":"142","author":"DH Matulionis","year":"1975","unstructured":"Matulionis DH (1975) Ultrastructural study of mouse olfactory epithelium following destruction by ZnSO4 and its subsequent regeneration. Am J Anat 142(1):67\u201389. https:\/\/doi.org\/10.1002\/aja.1001420106","journal-title":"Am J Anat"},{"issue":"8","key":"2902_CR46","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1093\/chemse\/bjg053","volume":"28","author":"K McBride","year":"2003","unstructured":"McBride K, Slotnick B, Margolis FL (2003) Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study. Chem Senses 28(8):659\u2013670. https:\/\/doi.org\/10.1093\/chemse\/bjg053","journal-title":"Chem Senses"},{"key":"2902_CR47","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2021.752320","author":"T Noto","year":"2021","unstructured":"Noto T, Zhou G, Yang Q, Lane G, Zelano C (2021) Human primary olfactory amygdala subregions form distinct functional networks, suggesting distinct olfactory functions. Front Syst Neurosci. https:\/\/doi.org\/10.3389\/fnsys.2021.752320","journal-title":"Front Syst Neurosci"},{"issue":"4","key":"2902_CR48","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/BF00688261","volume":"73","author":"TG Ohm","year":"1987","unstructured":"Ohm TG, Braak H (1987) Olfactory bulb changes in Alzheimer\u2019s disease. Acta Neuropathol 73(4):365\u2013369. https:\/\/doi.org\/10.1007\/BF00688261","journal-title":"Acta Neuropathol"},{"issue":"7","key":"2902_CR49","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.tips.2017.03.011","volume":"38","author":"ME Orr","year":"2017","unstructured":"Orr ME, Sullivan AC, Frost B (2017) A brief overview of tauopathy: causes, consequences, and therapeutic strategies. Trends Pharmacol Sci 38(7):637\u2013648. https:\/\/doi.org\/10.1016\/j.tips.2017.03.011","journal-title":"Trends Pharmacol Sci"},{"issue":"6","key":"2902_CR50","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1002\/jnr.490390607","volume":"39","author":"L Otvos Jr","year":"1994","unstructured":"Otvos L Jr, Feiner L, Lang E, Szendrei GI, Goedert M, Lee VM (1994) Monoclonal antibody PHF-1 recognizes tau protein phosphorylated at serine residues 396 and 404. J Neurosci Res 39(6):669\u2013673. https:\/\/doi.org\/10.1002\/jnr.490390607","journal-title":"J Neurosci Res"},{"issue":"1","key":"2902_CR51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/jad-190636","volume":"73","author":"M Parvand","year":"2020","unstructured":"Parvand M, Rankin CH (2020) Is there a shared etiology of olfactory impairments in normal aging and neurodegenerative disease? J Alzheimers Dis 73(1):1\u201321. https:\/\/doi.org\/10.3233\/jad-190636","journal-title":"J Alzheimers Dis"},{"issue":"1","key":"2902_CR52","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.pscychresns.2011.06.014","volume":"194","author":"SP Poulin","year":"2011","unstructured":"Poulin SP, Dautoff R, Morris JC, Barrett LF, Dickerson BC (2011) Amygdala atrophy is prominent in early Alzheimer\u2019s disease and relates to symptom severity. Psychiatry Res 194(1):7\u201313. https:\/\/doi.org\/10.1016\/j.pscychresns.2011.06.014","journal-title":"Psychiatry Res"},{"key":"2902_CR53","doi-asserted-by":"publisher","DOI":"10.1101\/2023.05.23.541792","author":"DMO Ramirez","year":"2023","unstructured":"Ramirez DMO, Whitesell JD, Bhagwat N, Thomas TL, Ajay AD, Nawaby A et al (2023) Endogenous pathology in tauopathy mice progresses via brain networks. bioRxiv. https:\/\/doi.org\/10.1101\/2023.05.23.541792","journal-title":"bioRxiv"},{"key":"2902_CR54","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.nbd.2016.12.013","volume":"109","author":"NL Rey","year":"2018","unstructured":"Rey NL, Wesson DW, Brundin P (2018) The olfactory bulb as the entry site for prion-like propagation in neurodegenerative diseases. Neurobiol Dis 109:226\u2013248. https:\/\/doi.org\/10.1016\/j.nbd.2016.12.013","journal-title":"Neurobiol Dis"},{"key":"2902_CR55","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2023.1149761","author":"N Sahara","year":"2023","unstructured":"Sahara N, Yanai R (2023) Limitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy. Front Neurosci. https:\/\/doi.org\/10.3389\/fnins.2023.1149761","journal-title":"Front Neurosci"},{"key":"2902_CR56","doi-asserted-by":"publisher","DOI":"10.1172\/jci168553","author":"N Samudra","year":"2023","unstructured":"Samudra N, Lane-Donovan C, VandeVrede L, Boxer AL (2023) Tau pathology in neurodegenerative disease: disease mechanisms and therapeutic avenues. J Clin Invest. https:\/\/doi.org\/10.1172\/jci168553","journal-title":"J Clin Invest"},{"key":"2902_CR57","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-19898-5","volume-title":"Neuroanatomy of the Mouse","author":"H Schr\u00f6der","year":"2020","unstructured":"Schr\u00f6der H, Moser N, Huggenberger S (2020) Neuroanatomy of the Mouse. Springer, Cham"},{"issue":"3","key":"2902_CR58","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1267\/ahc.22-00048","volume":"55","author":"S Shimizu","year":"2022","unstructured":"Shimizu S, Tojima I, Nakamura K, Kouzaki H, Kanesaka T, Ogawa N et al (2022) A Histochemical analysis of neurofibrillary tangles in olfactory epithelium, a study based on an autopsy case of juvenile Alzheimer\u2019s disease. Acta Histochem Cytochem 55(3):93\u201398. https:\/\/doi.org\/10.1267\/ahc.22-00048","journal-title":"Acta Histochem Cytochem"},{"key":"2902_CR59","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/b978-0-444-63855-7.00002-2","volume":"164","author":"TD Smith","year":"2019","unstructured":"Smith TD, Bhatnagar KP (2019) Anatomy of the olfactory system. Handb Clin Neurol 164:17\u201328. https:\/\/doi.org\/10.1016\/b978-0-444-63855-7.00002-2","journal-title":"Handb Clin Neurol"},{"issue":"6","key":"2902_CR60","doi-asserted-by":"publisher","first-page":"295","DOI":"10.5483\/BMBRep.2021.54.6.055","volume":"54","author":"G Son","year":"2021","unstructured":"Son G, Jahanshahi A, Yoo SJ, Boonstra JT, Hopkins DA, Steinbusch HWM et al (2021) Olfactory neuropathology in Alzheimer\u2019s disease: a sign of ongoing neurodegeneration. BMB Rep 54(6):295\u2013304. https:\/\/doi.org\/10.5483\/BMBRep.2021.54.6.055","journal-title":"BMB Rep"},{"issue":"1","key":"2902_CR61","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12974-020-01749-w","volume":"17","author":"Y Sun","year":"2020","unstructured":"Sun Y, Guo Y, Feng X, Jia M, Ai N, Dong Y et al (2020) The behavioural and neuropathologic sexual dimorphism and absence of MIP-3\u03b1 in tau P301S mouse model of Alzheimer\u2019s disease. J Neuroinflamm 17(1):72. https:\/\/doi.org\/10.1186\/s12974-020-01749-w","journal-title":"J Neuroinflamm"},{"key":"2902_CR62","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.neures.2014.02.012","volume":"84","author":"K Takehara-Nishiuchi","year":"2014","unstructured":"Takehara-Nishiuchi K (2014) Entorhinal cortex and consolidated memory. Neurosci Res 84:27\u201333. https:\/\/doi.org\/10.1016\/j.neures.2014.02.012","journal-title":"Neurosci Res"},{"issue":"6","key":"2902_CR63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021050","volume":"6","author":"H Takeuchi","year":"2011","unstructured":"Takeuchi H, Iba M, Inoue H, Higuchi M, Takao K, Tsukita K et al (2011) P301S mutant human tau transgenic mice manifest early symptoms of human tauopathies with dementia and altered sensorimotor gating. PLoS ONE 6(6):e21050. https:\/\/doi.org\/10.1371\/journal.pone.0021050","journal-title":"PLoS ONE"},{"key":"2902_CR64","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1749-6632.1991.tb00182.x","volume":"640","author":"BR Talamo","year":"1991","unstructured":"Talamo BR, Feng WH, Perez-Cruet M, Adelman L, Kosik K, Lee MY et al (1991) Pathologic changes in olfactory neurons in Alzheimer\u2019s disease. Ann N Y Acad Sci 640:1\u20137. https:\/\/doi.org\/10.1111\/j.1749-6632.1991.tb00182.x","journal-title":"Ann N Y Acad Sci"},{"issue":"5","key":"2902_CR65","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1046\/j.1365-2990.2003.00453.x","volume":"29","author":"Y Tsuboi","year":"2003","unstructured":"Tsuboi Y, Wszolek ZK, Graff-Radford NR, Cookson N, Dickson DW (2003) Tau pathology in the olfactory bulb correlates with Braak stage, Lewy body pathology and apolipoprotein epsilon4. Neuropathol Appl Neurobiol 29(5):503\u2013510. https:\/\/doi.org\/10.1046\/j.1365-2990.2003.00453.x","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"5","key":"2902_CR66","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1007\/s00424-021-02527-0","volume":"473","author":"WY Tzeng","year":"2021","unstructured":"Tzeng WY, Figarella K, Garaschuk O (2021) Olfactory impairment in men and mice related to aging and amyloid-induced pathology. Pfl\u00fcgers Arch Eur J Physiol 473(5):805\u2013821. https:\/\/doi.org\/10.1007\/s00424-021-02527-0","journal-title":"Pfl\u00fcgers Arch Eur J Physiol"},{"issue":"1","key":"2902_CR67","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40035-020-00200-7","volume":"9","author":"I Ubeda-Ba\u00f1on","year":"2020","unstructured":"Ubeda-Ba\u00f1on I, Saiz-Sanchez D, Flores-Cuadrado A, Rioja-Corroto E, Gonzalez-Rodriguez M, Villar-Conde S et al (2020) The human olfactory system in two proteinopathies Alzheimer\u2019s and Parkinson\u2019s diseases. Transl Neurodegener 9(1):22. https:\/\/doi.org\/10.1186\/s40035-020-00200-7","journal-title":"Transl Neurodegener"},{"issue":"1","key":"2902_CR68","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s40478-024-01907-8","volume":"12","author":"G Walkiewicz","year":"2024","unstructured":"Walkiewicz G, Ronisz A, Ospitalieri S, Tsaka G, Tom\u00e9 SO, Vandenberghe R et al (2024) pTau pathology in the retina of TAU58 mice: association with ganglion cell degeneration and implications on seeding and propagation of pTau from human brain lysates. Acta Neuropathol Commun 12(1):194. https:\/\/doi.org\/10.1186\/s40478-024-01907-8","journal-title":"Acta Neuropathol Commun"},{"issue":"4","key":"2902_CR69","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1002\/1098-1063(2000)10:4<398::AID-HIPO6>3.0.CO;2-K","volume":"10","author":"MP Witter","year":"2000","unstructured":"Witter MP, Naber PA, van Haeften T, Machielsen WCM, Rombouts S, Barkhof F et al (2000) Cortico-hippocampal communication by way of parallel parahippocampal-subicular pathways. Hippocampus 10(4):398\u2013410","journal-title":"Hippocampus"},{"key":"2902_CR70","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.neubiorev.2021.11.009","volume":"132","author":"Y Yan","year":"2022","unstructured":"Yan Y, Aierken A, Wang C, Song D, Ni J, Wang Z et al (2022) A potential biomarker of preclinical Alzheimer\u2019s disease: the olfactory dysfunction and its pathogenesis-based neural circuitry impairments. Neurosci Biobehav Rev 132:857\u2013869. https:\/\/doi.org\/10.1016\/j.neubiorev.2021.11.009","journal-title":"Neurosci Biobehav Rev"},{"issue":"6","key":"2902_CR71","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1111\/ejn.13333","volume":"44","author":"S Yang","year":"2016","unstructured":"Yang S, Kuan WL, Spillantini MG (2016) Progressive tauopathy in P301S tau transgenic mice is associated with a functional deficit of the olfactory system. Eur J Neurosci 44(6):2396\u20132403. https:\/\/doi.org\/10.1111\/ejn.13333","journal-title":"Eur J Neurosci"},{"issue":"3","key":"2902_CR72","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.neuron.2007.01.010","volume":"53","author":"Y Yoshiyama","year":"2007","unstructured":"Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC et al (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53(3):337\u2013351. https:\/\/doi.org\/10.1016\/j.neuron.2007.01.010","journal-title":"Neuron"},{"issue":"2","key":"2902_CR73","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14632","volume":"30","author":"H Yu","year":"2024","unstructured":"Yu H, Wang F, Jia D, Bi S, Gong J, Wu JJ et al (2024) Pathological features and molecular signatures of early olfactory dysfunction in 3xTg-AD model mice. CNS Neurosci Ther 30(2):e14632. https:\/\/doi.org\/10.1111\/cns.14632","journal-title":"CNS Neurosci Ther"},{"key":"2902_CR74","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12050607","author":"J Zhang","year":"2022","unstructured":"Zhang J, Zhao Z, Sun S, Li J, Wang Y, Dong J et al (2022) Olfactory evaluation in Alzheimer\u2019s disease model mice. Brain Sci. https:\/\/doi.org\/10.3390\/brainsci12050607","journal-title":"Brain Sci"},{"key":"2902_CR75","doi-asserted-by":"publisher","DOI":"10.3390\/biom13111568","author":"X Zhou","year":"2023","unstructured":"Zhou X, Kumar P, Bhuyan DJ, Jensen SO, Roberts TL, M\u00fcnch GW (2023) Neuroinflammation in Alzheimer\u2019s disease: a potential role of nose-picking in pathogen entry via the olfactory system? Biomolecules. https:\/\/doi.org\/10.3390\/biom13111568","journal-title":"Biomolecules"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-025-02902-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-025-02902-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-025-02902-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T08:57:36Z","timestamp":1750323456000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-025-02902-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,19]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["2902"],"URL":"https:\/\/doi.org\/10.1007\/s00401-025-02902-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.03.03.637437","asserted-by":"object"}]},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,19]]},"assertion":[{"value":"5 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"DRT and SOT received consultant honoraria from Muna Therapeutics. DRT collaborated with Novartis Pharma AG (Switzerland), and GE Healthcare (UK). The other authors have no competing interests to declare that are relevant to the content of this article.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All animal procedures were conducted in accordance with institutional and European guidelines and approved by the UCLouvain Ethical Committee for Animal Welfare\u00a0(2021\/UCL\/MD\/018). Human\n                      postmortem\n                      brain tissue was collected in accordance with the applicable legislation in Belgium. The recruitment protocols for the collection of human brains were approved by the ethical committee (2020\/02JUL\/355).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"64"}}