{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:07:23Z","timestamp":1791925643689,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The locus coeruleus (LC) provides dopamine\/noradrenaline (DA\/NA) innervation throughout the brain and undergoes early degeneration in Alzheimer's disease (AD). We evaluated catecholaminergic enzyme levels in the cerebrospinal fluid (CSF) of a group of patients biologically defined as within the AD continuum (ADc) and explored their relationship with AD biomarkers and cytokine\/growth factor levels to investigate their interplay with neurodegenerative and neuroinflammatory processes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The CSF concentration of DA transporter (DAT), tyrosine\u2010hydroxylase\u00a0(TH), DOPA\u2010decarboxylase (DDC), and dopamine\u2010\u03b2\u2010hydroxylase (D\u03b2H), as well as cytokine\/growth factor levels, were analyzed in 41 ADc patients stratified according to CSF beta\u2010amyloid (A\u03b2)<jats:sub>1\u201042<\/jats:sub> (A) and p\u2010tau\u00a0(T)\u00a0in\u00a0AD pathological changes\u00a0(A+\u00a0T\u2010) and AD\u00a0(A+\u00a0T+) subgroups, as well as in 15 control subjects (A\u2010\u00a0T\u2010).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The ADc group had lower CSF levels of DAT and TH but increased D\u03b2H levels to compensate for NA synthesis. DDC levels were higher in the A+\u2009T+ subgroup but comparable with controls in the A+ T\u2013 subgroup, probably because the DA system is resilient to the degeneration of LC neurons in the absence of tau pathology. Adjusting for age, sex, APOE genotype, and cognitive status, a significant association was found between TH and A\u03b2<jats:sub>1\u201042<\/jats:sub> (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.25) and between DDC and p\u2010tau (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.33). Finally, TH correlated with interleukin (IL)\u201010 levels (<jats:italic>p<\/jats:italic>\u00a0=\u20090.0008) and D\u03b2H with IL\u20101\u03b2 (<jats:italic>p<\/jats:italic>\u00a0=\u20090.03), IL\u20104 (<jats:italic>p<\/jats:italic>\u00a0=\u20090.02), granulocyte colony\u2010stimulating factor (<jats:italic>p<\/jats:italic>\u00a0=\u20090.007), and IL\u201017 (<jats:italic>p<\/jats:italic>\u00a0=\u20090.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these findings suggest that catecholaminergic enzymes, functional markers of the catecholaminergic system, are closely linked to the neurodegenerative and neuroinflammatory processes in AD pathology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.15691","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T13:45:58Z","timestamp":1674567958000},"page":"839-848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Interplay between the catecholaminergic enzymatic axis and neurodegeneration\/neuroinflammation processes in the Alzheimer's disease continuum"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6734-6979","authenticated-orcid":false,"given":"Caterina","family":"Motta","sequence":"first","affiliation":[{"name":"UOSD Centro Demenze, Department of Systems Medicine University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Assogna","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Department of Systems Medicine University of Rome \u201cTor Vergata\u201d  Rome Italy"},{"name":"Non\u2010Invasive Brain Stimulation Unit\/Department of Behavioral and Clinical Neurology Santa Lucia Foundation IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0881-8435","authenticated-orcid":false,"given":"Chiara Giuseppina","family":"Bonomi","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Department of Systems Medicine University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Di\u00a0Lorenzo","sequence":"additional","affiliation":[{"name":"Non\u2010Invasive Brain Stimulation Unit\/Department of Behavioral and Clinical Neurology Santa Lucia Foundation IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Nuccetelli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine University of Rome \"Tor Vergata\"  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Biagio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of Systems Medicine University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Koch","sequence":"additional","affiliation":[{"name":"Non\u2010Invasive Brain Stimulation Unit\/Department of Behavioral and Clinical Neurology Santa Lucia Foundation IRCCS  Rome Italy"},{"name":"Department of Neuroscience and Rehabilitation University of Ferrara  Ferrara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Martorana","sequence":"additional","affiliation":[{"name":"UOSD Centro Demenze, Department of Systems Medicine University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(85)90050-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2017.00080"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6486-11.2012"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.7b00078"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1616515114"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19325"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00220"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4236-05.2006"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909586107"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2019.08.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.28.061604.135709"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2015.07.004"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15045"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14727"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-180094"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.08.012"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.60"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.119"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay6931"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06622.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.01.010"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.005"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.05.008"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2014.00252"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-171018"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00925-1"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0770fje"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4265-05.2006"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0197-4580(98)00086-4"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2015.00067"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2985-10.2010"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-013-9480-6"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010751"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.12.015"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01901-5"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.06.007"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.9.6503"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205010666131120100743"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.03.015"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-011-9331-2"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109574"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14586"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.126"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.068"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191250"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1992.tb05108.x"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-022-06241-2"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.10372"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2022-329136"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15691","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.15691","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.15691","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T13:26:55Z","timestamp":1692710815000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.15691"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,14]]},"references-count":52,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/ene.15691"],"URL":"https:\/\/doi.org\/10.1111\/ene.15691","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,14]]},"assertion":[{"value":"2022-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}