{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T13:49:43Z","timestamp":1793713783344,"version":"4.6.1"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T00:00:00Z","timestamp":1649462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer\u2019s disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; <jats:italic>n<\/jats:italic>\u2009=\u200954) or dementia stage (<jats:italic>n<\/jats:italic>\u2009=\u2009240) and in cognitively unimpaired (<jats:italic>n<\/jats:italic>\u2009=\u2009113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (<jats:italic>n<\/jats:italic>\u2009=\u2009294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (<jats:italic>n<\/jats:italic>\u2009=\u2009113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and <jats:italic>APOE\u03b54<\/jats:italic> status verified the findings. In restricted analyses comparing A+T+ patients to A\u2212T\u2212 cognitively unimpaired, the findings for CSF adrenaline remained significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) but not for CSF noradrenaline (<jats:italic>p<\/jats:italic>\u2009=\u20090.07) and CSF dopamine (<jats:italic>p<\/jats:italic>\u2009=\u20090.33). There were no differences between A+T+ and A\u2212T\u2212 cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin.<\/jats:p>","DOI":"10.1038\/s41398-022-01901-5","type":"journal-article","created":{"date-parts":[[2022,4,9]],"date-time":"2022-04-09T13:04:34Z","timestamp":1649509474000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Cerebrospinal fluid catecholamines in Alzheimer\u2019s disease patients with and without biological disease"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9147-7282","authenticated-orcid":false,"given":"Kristi","family":"Henjum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiv Otto","family":"Watne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Godang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie Bodd","family":"Halaas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rannveig Saksholm","family":"Eldholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-4193","authenticated-orcid":false,"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-4354","authenticated-orcid":false,"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7897-9808","authenticated-orcid":false,"given":"Ingvild","family":"Saltvedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Bollerslev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-551X","authenticated-orcid":false,"given":"Anne Brita","family":"Knapskog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,9]]},"reference":[{"key":"1901_CR1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jalz.2012.11.007","volume":"9","author":"M Prince","year":"2013","unstructured":"Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimer\u2019s Dement. 2013;9:63\u201375.e62.","journal-title":"Alzheimer\u2019s Dement"},{"key":"1901_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2011.10.007","volume":"8","author":"BT Hyman","year":"2012","unstructured":"Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease. Alzheimer\u2019s Dement. 2012;8:1\u201313.","journal-title":"Alzheimer\u2019s Dement"},{"key":"1901_CR3","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/j.neubiorev.2013.05.008","volume":"37","author":"L Trillo","year":"2013","unstructured":"Trillo L, Das D, Hsieh W, Medina B, Moghadam S, Lin B, et al. Ascending monoaminergic systems alterations in Alzheimer\u2019s disease. translating basic science into clinical care. Neurosci Biobehav Rev. 2013;37:1363\u201379.","journal-title":"Neurosci Biobehav Rev"},{"key":"1901_CR4","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.pneurobio.2016.04.001","volume":"151","author":"G \u0160imi\u0107","year":"2017","unstructured":"\u0160imi\u0107 G, Babi\u0107 Leko M, Wray S, Harrington CR, Delalle I, Jovanov-Milo\u0161evi\u0107 N, et al. Monoaminergic neuropathology in Alzheimer\u2019s disease. Prog Neurobiol. 2017;151:101\u201338.","journal-title":"Prog Neurobiol"},{"key":"1901_CR5","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1177\/0269881113490326","volume":"27","author":"E Szabadi","year":"2013","unstructured":"Szabadi E. Functional neuroanatomy of the central noradrenergic system. J Psychopharmacol. 2013;27:659\u201393.","journal-title":"J Psychopharmacol"},{"key":"1901_CR6","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1146\/annurev.neuro.051508.135535","volume":"32","author":"TW Robbins","year":"2009","unstructured":"Robbins TW, Arnsten AF. The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu Rev Neurosci. 2009;32:267\u201387.","journal-title":"Annu Rev Neurosci"},{"key":"1901_CR7","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nrn2573","volume":"10","author":"SJ Sara","year":"2009","unstructured":"Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009;10:211\u201323.","journal-title":"Nat Rev Neurosci"},{"key":"1901_CR8","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/ni.3102","volume":"16","author":"MT Heneka","year":"2015","unstructured":"Heneka MT, Golenbock DT, Latz E. Innate immunity in Alzheimer\u2019s disease. Nat Immunol. 2015;16:229\u201336.","journal-title":"Nat Immunol"},{"key":"1901_CR9","doi-asserted-by":"publisher","first-page":"6058","DOI":"10.1073\/pnas.0909586107","volume":"107","author":"MT Heneka","year":"2010","unstructured":"Heneka MT, Nadrigny F, Regen T, Martinez-Hernandez A, Dumitrescu-Ozimek L, Terwel D, et al. Locus ceruleus controls Alzheimer\u2019s disease pathology by modulating microglial functions through norepinephrine. Proc Natl Acad Sci USA. 2010;107:6058\u201363.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1901_CR10","doi-asserted-by":"crossref","unstructured":"Matchett BJ, Grinberg LT, Theofilas P, Murray ME. The mechanistic link between selective vulnerability of the locus coeruleus and neurodegeneration in Alzheimer\u2019s disease. Acta Neuropathol. 2021;141:631\u201350.","DOI":"10.1007\/s00401-020-02248-1"},{"key":"1901_CR11","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1001\/archneur.60.3.337","volume":"60","author":"C Zarow","year":"2003","unstructured":"Zarow C, Lyness SA, Mortimer JA, Chui HC. Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases. Arch Neurol. 2003;60:337\u201341.","journal-title":"Arch Neurol"},{"key":"1901_CR12","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","volume":"70","author":"H Braak","year":"2011","unstructured":"Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70:960\u20139.","journal-title":"J Neuropathol Exp Neurol"},{"key":"1901_CR13","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.neurobiolaging.2018.07.007","volume":"71","author":"O Pletnikova","year":"2018","unstructured":"Pletnikova O, Kageyama Y, Rudow G, LaClair KD, Albert M, Crain BJ, et al. The spectrum of preclinical Alzheimer\u2019s disease pathology and its modulation by ApoE genotype. Neurobiol Aging. 2018;71:72\u201380.","journal-title":"Neurobiol Aging"},{"key":"1901_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-015-0187-1","volume":"3","author":"T Arendt","year":"2015","unstructured":"Arendt T, Br\u00fcckner MK, Morawski M, J\u00e4ger C, Gertz HJ. Early neurone loss in Alzheimer\u2019s disease: cortical or subcortical? Acta Neuropathol Commun. 2015;3:10.","journal-title":"Acta Neuropathol Commun"},{"key":"1901_CR15","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.jalz.2016.06.2362","volume":"13","author":"P Theofilas","year":"2017","unstructured":"Theofilas P, Ehrenberg AJ, Dunlop S, Di Lorenzo Alho AT, Nguy A, Leite REP, et al. Locus coeruleus volume and cell population changes during Alzheimer\u2019s disease progression: a stereological study in human postmortem brains with potential implication for early-stage biomarker discovery. Alzheimer\u2019s Dement. 2017;13:236\u201346.","journal-title":"Alzheimer\u2019s Dement"},{"key":"1901_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-017-0411-2","volume":"5","author":"SC Kelly","year":"2017","unstructured":"Kelly SC, He B, Perez SE, Ginsberg SD, Mufson EJ, Counts SE. Locus coeruleus cellular and molecular pathology during the progression of Alzheimer\u2019s disease. Acta Neuropathol Commun. 2017;5:8.","journal-title":"Acta Neuropathol Commun"},{"key":"1901_CR17","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1111\/nan.12386","volume":"43","author":"P Andr\u00e9s-Benito","year":"2017","unstructured":"Andr\u00e9s-Benito P, Fern\u00e1ndez-Due\u00f1as V, Carmona M, Escobar LA, Torrej\u00f3n-Escribano B, Aso E, et al. Locus coeruleus at asymptomatic early and middle Braak stages of neurofibrillary tangle pathology. Neuropathol Appl Neurobiol. 2017;43:373\u201392.","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1901_CR18","doi-asserted-by":"publisher","first-page":"R187","DOI":"10.1152\/ajpregu.00054.2013","volume":"305","author":"PG Guyenet","year":"2013","unstructured":"Guyenet PG, Stornetta RL, Bochorishvili G, Depuy SD, Burke PG, Abbott SB. C1 neurons: the body\u2019s EMTs. Am J Physiol Regul Integr Comp Physiol. 2013;305:R187\u2013204.","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"1901_CR19","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.phrs.2018.01.016","volume":"130","author":"M D\u2019Amelio","year":"2018","unstructured":"D\u2019Amelio M, Puglisi-Allegra S, Mercuri N. The role of dopaminergic midbrain in Alzheimer\u2019s disease: translating basic science into clinical practice. Pharm Res. 2018;130:414\u20139.","journal-title":"Pharm Res"},{"key":"1901_CR20","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1136\/jnnp.52.2.193","volume":"52","author":"WR Gibb","year":"1989","unstructured":"Gibb WR, Mountjoy CQ, Mann DM, Lees AJ. The substantia nigra and ventral tegmental area in Alzheimer\u2019s disease and Down\u2019s syndrome. J Neurol Neurosurg Psychiatry. 1989;52:193\u2013200.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1901_CR21","doi-asserted-by":"publisher","first-page":"2798","DOI":"10.1093\/brain\/aws211","volume":"135","author":"SJ Colloby","year":"2012","unstructured":"Colloby SJ, McParland S, O\u2019Brien JT, Attems J. Neuropathological correlates of dopaminergic imaging in Alzheimer\u2019s disease and Lewy body dementias. Brain. 2012;135:2798\u2013808.","journal-title":"Brain"},{"key":"1901_CR22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neurobiolaging.2020.12.009","volume":"99","author":"T Miyagawa","year":"2021","unstructured":"Miyagawa T, Przybelski SA, Maltais D, Min HK, Jordan L, Lesnick TG, et al. The value of multimodal imaging with (123)I-FP-CIT SPECT in differential diagnosis of dementia with Lewy bodies and Alzheimer\u2019s disease dementia. Neurobiol Aging. 2021;99:11\u201318.","journal-title":"Neurobiol Aging"},{"key":"1901_CR23","doi-asserted-by":"publisher","first-page":"14727","DOI":"10.1038\/ncomms14727","volume":"8","author":"A Nobili","year":"2017","unstructured":"Nobili A, Latagliata EC, Viscomi MT, Cavallucci V, Cutuli D, Giacovazzo G, et al. Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer\u2019s disease. Nat Commun. 2017;8:14727.","journal-title":"Nat Commun"},{"key":"1901_CR24","doi-asserted-by":"publisher","first-page":"167","DOI":"10.3233\/JAD-171018","volume":"63","author":"M De Marco","year":"2018","unstructured":"De Marco M, Venneri A. Volume and connectivity of the ventral tegmental area are linked to neurocognitive signatures of Alzheimer\u2019s disease in humans. J Alzheimers Dis. 2018;63:167\u201380.","journal-title":"J Alzheimers Dis"},{"key":"1901_CR25","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","volume":"87","author":"CR Jack Jr.","year":"2016","unstructured":"Jack CR Jr., Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A\/T\/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87:539\u201347.","journal-title":"Neurology"},{"key":"1901_CR26","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr.","year":"2018","unstructured":"Jack CR Jr., Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimer\u2019s Dement. 2018;14:535\u201362.","journal-title":"Alzheimer\u2019s Dement"},{"key":"1901_CR27","doi-asserted-by":"publisher","first-page":"11232","DOI":"10.1073\/pnas.210184697","volume":"97","author":"JH Pak","year":"2000","unstructured":"Pak JH, Huang FL, Li J, Balschun D, Reymann KG, Chiang C, et al. Involvement of neurogranin in the modulation of calcium\/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: a study with knockout mice. Proc Natl Acad Sci USA. 2000;97:11232\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1901_CR28","doi-asserted-by":"publisher","first-page":"3782","DOI":"10.1523\/JNEUROSCI.10-12-03782.1990","volume":"10","author":"A Represa","year":"1990","unstructured":"Represa A, Deloulme JC, Sensenbrenner M, Ben-Ari Y, Baudier J. Neurogranin: immunocytochemical localization of a brain-specific protein kinase C substrate. J Neurosci. 1990;10:3782\u201392.","journal-title":"J Neurosci"},{"key":"1901_CR29","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1007\/s00401-018-1851-x","volume":"136","author":"E Portelius","year":"2018","unstructured":"Portelius E, Olsson B, Hoglund K, Cullen NC, Kvartsberg H, Andreasson U, et al. Cerebrospinal fluid neurogranin concentration in neurodegeneration: relation to clinical phenotypes and neuropathology. Acta Neuropathol. 2018;136:363\u201376.","journal-title":"Acta Neuropathol"},{"key":"1901_CR30","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1212\/WNL.0000000000002423","volume":"86","author":"H Wellington","year":"2016","unstructured":"Wellington H, Paterson RW, Portelius E, T\u00f6rnqvist U, Magdalinou N, Fox NC, et al. Increased CSF neurogranin concentration is specific to Alzheimer disease. Neurology. 2016;86:829\u201335.","journal-title":"Neurology"},{"key":"1901_CR31","unstructured":"Bogdanovic N, Davidsson P, Gottfries J, Volkman I, Winblad B, Blennow K. Regional and cellular distribution of synaptic proteins in the normal human brain. Brain Aging. 2002;2:18\u201330."},{"key":"1901_CR32","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1001\/archpsyc.1984.01790150033006","volume":"41","author":"MA Raskind","year":"1984","unstructured":"Raskind MA, Peskind ER, Halter JB, Jimerson DC. Norepinephrine and MHPG levels in CSF and plasma in Alzheimer\u2019s disease. Arch Gen Psychiatry. 1984;41:343\u20136.","journal-title":"Arch Gen Psychiatry"},{"key":"1901_CR33","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/BF03159966","volume":"16","author":"L Parnetti","year":"1992","unstructured":"Parnetti L, Gaiti A, Reboldi GP, Santucci C, Mecocci P, Brunetti M, et al. CSF monoamine metabolites in old age dementias. Mol Chem Neuropathol. 1992;16:143\u201357.","journal-title":"Mol Chem Neuropathol"},{"key":"1901_CR34","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1176\/ajp.154.1.25","volume":"154","author":"R Elrod","year":"1997","unstructured":"Elrod R, Peskind ER, DiGiacomo L, Brodkin KI, Veith RC, Raskind MA. Effects of Alzheimer\u2019s disease severity on cerebrospinal fluid norepinephrine concentration. Am J Psychiatry. 1997;154:25\u201330.","journal-title":"Am J Psychiatry"},{"key":"1901_CR35","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3389\/fnagi.2015.00067","volume":"7","author":"A Stefani","year":"2015","unstructured":"Stefani A, Olivola E, Liguori C, Hainsworth AH, Saviozzi V, Angileri G, et al. Catecholamine-based treatment in AD patients: expectations and delusions. Front Aging Neurosci. 2015;7:67.","journal-title":"Front Aging Neurosci"},{"key":"1901_CR36","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/S0893-133X(98)00054-2","volume":"19","author":"ER Peskind","year":"1998","unstructured":"Peskind ER, Elrod R, Dobie DJ, Pascualy M, Petrie E, Jensen C, et al. Cerebrospinal fluid epinephrine in Alzheimer\u2019s disease and normal aging. Neuropsychopharmacology. 1998;19:465\u201371.","journal-title":"Neuropsychopharmacology"},{"key":"1901_CR37","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/0197-4580(92)90017-R","volume":"13","author":"K Blennow","year":"1992","unstructured":"Blennow K, Wallin A, Gottfries CG, Lekman A, Karlsson I, Skoog I, et al. Significance of decreased lumbar CSF levels of HVA and 5-HIAA in Alzheimer\u2019s disease. Neurobiol Aging. 1992;13:107\u201313.","journal-title":"Neurobiol Aging"},{"key":"1901_CR38","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1002\/ana.410270502","volume":"27","author":"ST DeKosky","year":"1990","unstructured":"DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer\u2019s disease: correlation with cognitive severity. Ann Neurol. 1990;27:457\u201364.","journal-title":"Ann Neurol"},{"key":"1901_CR39","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","volume":"7","author":"MS Albert","year":"2011","unstructured":"Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement. 2011;7:270\u20139.","journal-title":"Alzheimers Dement"},{"key":"1901_CR40","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR, Kawas CH, et al. The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement. 2011;7:263\u20139.","journal-title":"Alzheimers Dement"},{"key":"1901_CR41","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.4045\/tidsskr.11.0786","volume":"131","author":"A Br\u00e6khus","year":"2011","unstructured":"Br\u00e6khus A, Ulstein I, Wyller TB, Engedal K. The Memory Clinic\u2014outpatient assessment when dementia is suspected. Tidsskr Nor Laegeforen. 2011;131:2254\u20137.","journal-title":"Tidsskr Nor Laegeforen"},{"key":"1901_CR42","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/BF02815140","volume":"26","author":"K Blennow","year":"1995","unstructured":"Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol. 1995;26:231\u201345.","journal-title":"Mol Chem Neuropathol"},{"key":"1901_CR43","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3109\/13506120009146438","volume":"7","author":"H Vanderstichele","year":"2000","unstructured":"Vanderstichele H, Van KE, Hesse C, Davidsson P, Buyse MA, Andreasen N, et al. Standardization of measurement of beta-amyloid(1-42) in cerebrospinal fluid and plasma. Amyloid. 2000;7:245\u201358.","journal-title":"Amyloid"},{"key":"1901_CR44","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1001\/archneur.56.6.673","volume":"56","author":"N Andreasen","year":"1999","unstructured":"Andreasen N, Hesse C, Davidsson P, Minthon L, Wallin A, Winblad B, et al. Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch Neurol. 1999;56:673\u201380.","journal-title":"Arch Neurol"},{"key":"1901_CR45","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.neurobiolaging.2016.09.012","volume":"49","author":"AV Idland","year":"2017","unstructured":"Idland AV, Sala-Llonch R, Borza T, Watne LO, Wyller TB, Braekhus A, et al. CSF neurofilament light levels predict hippocampal atrophy in cognitively healthy older adults. Neurobiol Aging. 2017;49:138\u201344.","journal-title":"Neurobiol Aging"},{"key":"1901_CR46","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/S1474-4422(06)70355-6","volume":"5","author":"O Hansson","year":"2006","unstructured":"Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer\u2019s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5:228\u201334.","journal-title":"Lancet Neurol"},{"key":"1901_CR47","doi-asserted-by":"crossref","unstructured":"Henjum K, Godang K, Quist-Paulsen E, Idland A-V, Neerland BE, Sandvig H, et al. Cerebrospinal fluid catecholamines in delirium and dementia. Brain Commun. 2021;3:fcab121.","DOI":"10.1093\/braincomms\/fcab121"},{"key":"1901_CR48","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1001\/jamaneurol.2015.1867","volume":"72","author":"MI Kester","year":"2015","unstructured":"Kester MI, Teunissen CE, Crimmins DL, Herries EM, Ladenson JH, Scheltens P, et al. Neurogranin as a cerebrospinal fluid biomarker for synaptic loss in symptomatic Alzheimer disease. JAMA Neurol. 2015;72:1275\u201380.","journal-title":"JAMA Neurol"},{"key":"1901_CR49","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1113\/jphysiol.2012.232157","volume":"590","author":"SB Abbott","year":"2012","unstructured":"Abbott SB, Kanbar R, Bochorishvili G, Coates MB, Stornetta RL, Guyenet PG. C1 neurons excite locus coeruleus and A5 noradrenergic neurons along with sympathetic outflow in rats. J Physiol. 2012;590:2897\u2013915.","journal-title":"J Physiol"},{"key":"1901_CR50","doi-asserted-by":"publisher","first-page":"18792","DOI":"10.1523\/JNEUROSCI.2916-13.2013","volume":"33","author":"BB Holloway","year":"2013","unstructured":"Holloway BB, Stornetta RL, Bochorishvili G, Erisir A, Viar KE, Guyenet PG. Monosynaptic glutamatergic activation of locus coeruleus and other lower brainstem noradrenergic neurons by the C1 cells in mice. J Neurosci. 2013;33:18792\u2013805.","journal-title":"J Neurosci"},{"key":"1901_CR51","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/S0006-3223(99)00008-6","volume":"46","author":"MA Raskind","year":"1999","unstructured":"Raskind MA, Peskind ER, Holmes C, Goldstein DS. Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer\u2019s disease. Biol Psychiatry. 1999;46:756\u201365.","journal-title":"Biol Psychiatry"},{"key":"1901_CR52","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13195-015-0124-3","volume":"7","author":"H Kvartsberg","year":"2015","unstructured":"Kvartsberg H, Portelius E, Andreasson U, Brinkmalm G, Hellwig K, Lelental N, et al. Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer\u2019s disease patients and healthy controls. Alzheimers Res Ther. 2015;7:40.","journal-title":"Alzheimers Res Ther"},{"key":"1901_CR53","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1097\/WCO.0b013e32835a3432","volume":"25","author":"H Braak","year":"2012","unstructured":"Braak H, Del Tredici K. Where, when, and in what form does sporadic Alzheimer\u2019s disease begin? Curr Opin Neurol. 2012;25:708\u201314.","journal-title":"Curr Opin Neurol"},{"key":"1901_CR54","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1523\/JNEUROSCI.4265-05.2006","volume":"26","author":"P Szot","year":"2006","unstructured":"Szot P, White SS, Greenup JL, Leverenz JB, Peskind ER, Raskind MA. Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer\u2019s disease and dementia with Lewy bodies. J Neurosci. 2006;26:467\u201378.","journal-title":"J Neurosci"},{"key":"1901_CR55","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1002\/1531-8249(199901)45:1<82::AID-ART14>3.0.CO;2-T","volume":"45","author":"WJ Hoogendijk","year":"1999","unstructured":"Hoogendijk WJ, Feenstra MG, Botterblom MH, Gilhuis J, Sommer IE, Kamphorst W, et al. Increased activity of surviving locus ceruleus neurons in Alzheimer\u2019s disease. Ann Neurol. 1999;45:82\u201391.","journal-title":"Ann Neurol"},{"key":"1901_CR56","doi-asserted-by":"crossref","unstructured":"Jacobs HIL, Riphagen JM, Ramakers I, Verhey FRJ. Alzheimer\u2019s disease pathology: pathways between central norepinephrine activity, memory, and neuropsychiatric symptoms. Mol Psychiatry. 2019;26:897\u2013906.","DOI":"10.1038\/s41380-019-0437-x"},{"key":"1901_CR57","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1016\/j.neuropsychologia.2009.03.004","volume":"47","author":"Y Stern","year":"2009","unstructured":"Stern Y. Cognitive reserve. Neuropsychologia. 2009;47:2015\u201328.","journal-title":"Neuropsychologia"},{"key":"1901_CR58","first-page":"172","volume":"10","author":"J Janssens","year":"2018","unstructured":"Janssens J, Vermeiren Y, Fransen E, Aerts T, Van Dam D, Engelborghs S, et al. Cerebrospinal fluid and serum MHPG improve Alzheimer\u2019s disease versus dementia with Lewy bodies differential diagnosis. Alzheimer\u2019s Dement. 2018;10:172\u201381.","journal-title":"Alzheimer\u2019s Dement"},{"key":"1901_CR59","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1111\/ggi.12280","volume":"15","author":"J Takahashi","year":"2015","unstructured":"Takahashi J, Shibata T, Sasaki M, Kudo M, Yanezawa H, Obara S, et al. Detection of changes in the locus coeruleus in patients with mild cognitive impairment and Alzheimer\u2019s disease: high-resolution fast spin-echo T1-weighted imaging. Geriatr Gerontol Int. 2015;15:334\u201340.","journal-title":"Geriatr Gerontol Int"},{"key":"1901_CR60","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.neuint.2019.04.015","volume":"128","author":"J Janssens","year":"2019","unstructured":"Janssens J, Atmosoerodjo SD, Vermeiren Y, Absalom AR, den Daas I, De Deyn PP. Sampling issues of cerebrospinal fluid and plasma monoamines: investigation of the circadian rhythm and rostrocaudal concentration gradient. Neurochem Int. 2019;128:154\u201362.","journal-title":"Neurochem Int"},{"key":"1901_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-0841-7","volume":"10","author":"LE Pillet","year":"2020","unstructured":"Pillet LE, Taccola C, Cotoni J, Thiriez H, Andr\u00e9 K, Verpillot R. Correlation between cognition and plasma noradrenaline level in Alzheimer\u2019s disease: a potential new blood marker of disease evolution. Transl psychiatry. 2020;10:213.","journal-title":"Transl psychiatry"},{"key":"1901_CR62","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1192\/bjp.135.3.216","volume":"135","author":"R Adolfsson","year":"1979","unstructured":"Adolfsson R, Gottfries CG, Roos BE, Winblad B. Changes in the brain catecholamines in patients with dementia of Alzheimer type. Br J Psychiatry. 1979;135:216\u201323.","journal-title":"Br J Psychiatry"},{"key":"1901_CR63","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/S0197-4580(98)00086-4","volume":"19","author":"M Sj\u00f6gren","year":"1998","unstructured":"Sj\u00f6gren M, Minthon L, Passant U, Blennow K, Wallin A. Decreased monoamine metabolites in frontotemporal dementia and Alzheimer\u2019s disease. Neurobiol Aging. 1998;19:379\u201384.","journal-title":"Neurobiol Aging"},{"key":"1901_CR64","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/ana.21610","volume":"65","author":"LM Shaw","year":"2009","unstructured":"Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, et al. Cerebrospinal fluid biomarker signature in Alzheimer\u2019s disease neuroimaging initiative subjects. Ann Neurol. 2009;65:403\u201313.","journal-title":"Ann Neurol"},{"key":"1901_CR65","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.neuint.2009.02.017","volume":"55","author":"K Koopman","year":"2009","unstructured":"Koopman K, Le Bastard N, Martin JJ, Nagels G, De Deyn PP, Engelborghs S. Improved discrimination of autopsy-confirmed Alzheimer\u2019s disease (AD) from non-AD dementias using CSF P-tau(181P). Neurochem Int. 2009;55:214\u20138.","journal-title":"Neurochem Int"},{"key":"1901_CR66","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s00401-010-0654-5","volume":"119","author":"KA Jellinger","year":"2010","unstructured":"Jellinger KA, Attems J. Prevalence of dementia disorders in the oldest-old: an autopsy study. Acta Neuropathol. 2010;119:421\u201333.","journal-title":"Acta Neuropathol"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-022-01901-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-022-01901-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-022-01901-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T19:24:48Z","timestamp":1669231488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-022-01901-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,9]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1901"],"URL":"https:\/\/doi.org\/10.1038\/s41398-022-01901-5","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,9]]},"assertion":[{"value":"17 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"ABK has been\/is a principal investigator in Roche drug trials BN29553 and Novo Nordisk, NN6535-4730, and ABK and IS in Boehringer-Ingelheim drug trial 1346.0023. IS has been a consultant at the advisory board for Biogen. K.B. has worked as a consultant or at advisory boards or at data monitoring committees for Abcam, Axon, Biogen, JOMDD\/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. H.Z. has served at scientific advisory boards for Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, and CogRx, and has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, and Biogen. KB and HZ are co-founders of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg. The other authors have no conflicts of interest to report.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"151"}}