{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:13:08Z","timestamp":1789989188546,"version":"4.0.1"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To explore markers for synaptic function and Alzheimer disease (AD) pathology in late life depression (LLD), predementia AD and normal controls (NC). A cross-sectional study to compare cerebrospinal fluid (CSF) levels of neurogranin (Ng), Beta-site amyloid-precursor-protein cleaving enzyme1 (BACE1), Ng\/BACE1 ratio and Amyloid-\u03b2 42\/40 ratio, phosphorylated-tau and total-tau in LLD with (LLD AD) or without (LLD NoAD) AD pathology, predementia AD and normal controls (NC). We included 145 participants (NC\u2009=\u200941; predementia AD\u2009=\u200966 and LLD\u2009=\u200938). LLD comprised LLD AD (n\u2009=\u200916), LLD NoAD (n\u2009=\u200919), LLD with non-AD typical changes (n\u2009=\u20093, excluded). LLD AD (p<jats:sub>ADJ<\/jats:sub>\u2009&lt;\u20090.05) and predementia AD (p<jats:sub>ADJ<\/jats:sub>\u2009&lt;\u20090.0001) showed significantly higher Ng than NC. BACE1 and Ng\/BACE1 ratio were altered similarly. Compared to LLD NoAD, LLD AD showed significantly higher Ng (p<jats:sub>ADJ<\/jats:sub>\u2009&lt;\u20090.001), BACE1 (p<jats:sub>ADJ<\/jats:sub>\u2009&lt;\u20090.05) and Ng\/BACE1 ratio (p<jats:sub>ADJ<\/jats:sub>\u2009&lt;\u20090.01). All groups had significantly lower A\u03b2 42\/40 ratio than NC (predementia AD and LLD AD, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001; LLD NoAD, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Both LLD groups performed similarly on tests of memory and executive function, but significantly poorer than NC. Synaptic function in LLD depended on AD pathology. LLD showed an association to Amyloid dysmetabolism. The LLD groups performed poorer cognitively than NC. LLD AD may be conceptualized as \u201cpredementia AD with depression\u201d.<\/jats:p>","DOI":"10.1038\/s41598-021-99794-9","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T17:43:34Z","timestamp":1634147014000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Cerebrospinal fluid markers for synaptic function and Alzheimer type changes in late life depression"],"prefix":"10.1038","volume":"11","author":[{"given":"Nikias","family":"Siafarikas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f8rn-Eivind","family":"Kirsebom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak P.","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia M.","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirik","family":"Auning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Hessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geir","family":"Selbaek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tormod","family":"Fladby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"issue":"1\u20133","key":"99794_CR1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jad.2010.09.015","volume":"129","author":"TW Meeks","year":"2011","unstructured":"Meeks, T. W. et al. A tune in \u201ca minor\u201d can \u201cb major\u201d: A review of epidemiology, illness course, and public health implications of subthreshold depression in older adults. J. Affect. Disord. 129(1\u20133), 126\u2013142 (2011).","journal-title":"J. Affect. Disord."},{"issue":"7","key":"99794_CR2","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s00702-012-0945-1","volume":"120","author":"KA Jellinger","year":"2013","unstructured":"Jellinger, K. A. Organic bases of late-life depression: A critical update. J. Neural Transm. 120(7), 1109\u20131125 (2013).","journal-title":"J. Neural Transm."},{"issue":"10043","key":"99794_CR3","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0140-6736(15)01124-1","volume":"388","author":"P Scheltens","year":"2016","unstructured":"Scheltens, P. et al. Alzheimer\u2019s disease. Lancet 388(10043), 505\u2013517 (2016).","journal-title":"Lancet"},{"issue":"3","key":"99794_CR4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jagp.2015.12.003","volume":"24","author":"N Mahgoub","year":"2016","unstructured":"Mahgoub, N. & Alexopoulos, G. S. Amyloid hypothesis: Is there a role for antiamyloid treatment in late-life depression?. Am. J. Geriatr. Psychiatry 24(3), 239\u2013247 (2016).","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"99794_CR5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jpsychires.2015.07.024","volume":"69","author":"KK Nascimento","year":"2015","unstructured":"Nascimento, K. K. et al. Plasma and cerebrospinal fluid amyloid-beta levels in late-life depression: A systematic review and meta-analysis. J. Psychiatr. Res. 69, 35\u201341 (2015).","journal-title":"J. Psychiatr. Res."},{"issue":"1","key":"99794_CR6","doi-asserted-by":"crossref","first-page":"15981","DOI":"10.1038\/s41598-021-95206-0","volume":"11","author":"A Takamiya","year":"2021","unstructured":"Takamiya, A. et al. Lower regional gray matter volume in the absence of higher cortical amyloid burden in late-life depression. Sci. Rep. 11(1), 15981 (2021).","journal-title":"Sci. Rep."},{"issue":"6","key":"99794_CR7","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.neuron.2005.10.028","volume":"48","author":"JR Cirrito","year":"2005","unstructured":"Cirrito, J. R. et al. Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo. Neuron 48(6), 913\u2013922 (2005).","journal-title":"Neuron"},{"key":"99794_CR8","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.pharmthera.2018.11.006","volume":"195","author":"Y Chen","year":"2019","unstructured":"Chen, Y., Fu, A. K. Y. & Ip, N. Y. Synaptic dysfunction in Alzheimer\u2019s disease: Mechanisms and therapeutic strategies. Pharmacol. Ther. 195, 186\u2013198 (2019).","journal-title":"Pharmacol. Ther."},{"issue":"12","key":"99794_CR9","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/iub.1099","volume":"64","author":"E Tamagno","year":"2012","unstructured":"Tamagno, E. et al. Transcriptional and post-transcriptional regulation of beta-secretase. IUBMB Life 64(12), 943\u2013950 (2012).","journal-title":"IUBMB Life"},{"key":"99794_CR10","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1172\/JCI133737","volume":"130","author":"ER Roy","year":"2020","unstructured":"Roy, E. R. et al. Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease. J. Clin. Invest. 130, 1912\u20131930 (2020).","journal-title":"J. Clin. Invest."},{"key":"99794_CR11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s00401-018-1851-x","volume":"136","author":"E Portelius","year":"2018","unstructured":"Portelius, E. et al. Cerebrospinal fluid neurogranin concentration in neurodegeneration: Relation to clinical phenotypes and neuropathology. Acta Neuropathol. 136, 363\u2013376 (2018).","journal-title":"Acta Neuropathol."},{"issue":"1","key":"99794_CR12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/cne.20302","volume":"479","author":"I Singec","year":"2004","unstructured":"Singec, I. et al. Neurogranin is expressed by principal cells but not interneurons in the rodent and monkey neocortex and hippocampus. J. Comp. Neurol. 479(1), 30\u201342 (2004).","journal-title":"J. Comp. Neurol."},{"issue":"10","key":"99794_CR13","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1007\/s00018-019-03040-5","volume":"76","author":"K Dhiman","year":"2019","unstructured":"Dhiman, K. et al. Cerebrospinal fluid biomarkers for understanding multiple aspects of Alzheimer\u2019s disease pathogenesis. Cell Mol. Life Sci. 76(10), 1833\u20131863 (2019).","journal-title":"Cell Mol. Life Sci."},{"issue":"19","key":"99794_CR14","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1038\/emboj.2009.236","volume":"28","author":"L Zhong","year":"2009","unstructured":"Zhong, L. et al. Neurogranin enhances synaptic strength through its interaction with calmodulin. EMBO J. 28(19), 3027\u20133039 (2009).","journal-title":"EMBO J."},{"key":"99794_CR15","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1007\/s40520-019-01326-z","volume":"32","author":"IA Mavroudis","year":"2019","unstructured":"Mavroudis, I. A. et al. A meta-analysis on CSF neurogranin levels for the diagnosis of Alzheimer\u2019s disease and mild cognitive impairment. Aging Clin. Exp. Res. 32, 1639\u20131646 (2019).","journal-title":"Aging Clin. Exp. Res."},{"issue":"12","key":"99794_CR16","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1007\/s00702-016-1597-3","volume":"123","author":"C Sanfilippo","year":"2016","unstructured":"Sanfilippo, C. et al. Increased neurogranin concentrations in cerebrospinal fluid of Alzheimer\u2019s disease and in mild cognitive impairment due to AD. J. Neural Transm. 123(12), 1443\u20131447 (2016).","journal-title":"J. Neural Transm."},{"issue":"2","key":"99794_CR17","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1159\/000489847","volume":"8","author":"CG Schipke","year":"2018","unstructured":"Schipke, C. G. et al. Neurogranin and BACE1 in CSF as potential biomarkers differentiating depression with cognitive deficits from early Alzheimer\u2019s disease: A pilot study. Dement Geriatr. Cogn. Disord. Extra 8(2), 277\u2013289 (2018).","journal-title":"Dement Geriatr. Cogn. Disord. Extra"},{"issue":"1","key":"99794_CR18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3233\/JAD-170231","volume":"60","author":"T Fladby","year":"2017","unstructured":"Fladby, T. et al. Detecting at-risk Alzheimer\u2019s disease cases. J. Alzheimers Dis. 60(1), 97\u2013105 (2017).","journal-title":"J. Alzheimers Dis."},{"key":"99794_CR19","volume-title":"The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines","author":"WHO","year":"1992","unstructured":"WHO. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines (WHO, 1992)."},{"issue":"Suppl 20","key":"99794_CR20","first-page":"22","volume":"59","author":"DV Sheehan","year":"1998","unstructured":"Sheehan, D. V. et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 59(Suppl 20), 22\u201333 (1998).","journal-title":"J. Clin. Psychiatry"},{"issue":"2","key":"99794_CR21","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1176\/jnp.12.2.233","volume":"12","author":"DI Kaufer","year":"2000","unstructured":"Kaufer, D. I. et al. Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J. Neuropsychiatry Clin. Neurosci. 12(2), 233\u2013239 (2000).","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"99794_CR22","doi-asserted-by":"crossref","unstructured":"Sheikh, J. I. & Yesavage, J. A. Geriatric depression scale (GDS): Recent evidence and development of a shorter version. 1986.","DOI":"10.1037\/t01786-000"},{"key":"99794_CR23","volume-title":"The ICD-10 Classification of Mental and Behavioural Disorders Diagnostic Criteria for Research; ICD-10","author":"World Health Organization","year":"1993","unstructured":"World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders Diagnostic Criteria for Research; ICD-10 (WHO, 1993)."},{"issue":"4","key":"99794_CR24","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.psc.2013.08.010","volume":"36","author":"Z Ismail","year":"2013","unstructured":"Ismail, Z., Fischer, C. & McCall, W. V. What characterizes late-life depression?. Psychiatr. Clin. North Am. 36(4), 483\u2013496 (2013).","journal-title":"Psychiatr. Clin. North Am."},{"issue":"4","key":"99794_CR25","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.psc.2013.08.001","volume":"36","author":"R Aziz","year":"2013","unstructured":"Aziz, R. & Steffens, D. C. What are the causes of late-life depression?. Psychiatr. Clin. North Am. 36(4), 497\u2013516 (2013).","journal-title":"Psychiatr. Clin. North Am."},{"issue":"6","key":"99794_CR26","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.jalz.2014.01.001","volume":"10","author":"F Jessen","year":"2014","unstructured":"Jessen, F. et al. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer\u2019s disease. Alzheimers Dement. 10(6), 844\u2013852 (2014).","journal-title":"Alzheimers Dement."},{"issue":"3","key":"99794_CR27","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jalz.2011.03.008","volume":"7","author":"MS Albert","year":"2011","unstructured":"Albert, M. S. 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. 7(3), 270\u2013279 (2011).","journal-title":"Alzheimers Dement."},{"issue":"3","key":"99794_CR28","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein, M. F., Folstein, S. E. & McHugh, P. R. \u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12(3), 189\u2013198 (1975).","journal-title":"J. Psychiatr. Res."},{"issue":"6","key":"99794_CR29","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1002\/1099-1166(200006)15:6<548::AID-GPS242>3.0.CO;2-U","volume":"15","author":"KI Shulman","year":"2000","unstructured":"Shulman, K. I. Clock-drawing: Is it the ideal cognitive screening test?. Int. J. Geriatr. Psychiatry 15(6), 548\u2013561 (2000).","journal-title":"Int. J. Geriatr. Psychiatry"},{"issue":"2","key":"99794_CR30","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jalz.2007.08.005","volume":"4","author":"GG Fillenbaum","year":"2008","unstructured":"Fillenbaum, G. G. et al. Consortium to establish a registry for Alzheimer\u2019s disease (CERAD): The first twenty years. Alzheimers Dement. 4(2), 96\u2013109 (2008).","journal-title":"Alzheimers Dement."},{"key":"99794_CR31","volume-title":"The Halstead\u2013Reitan Neuropsychological Test Battery: Theory and Clinical Interpretation","author":"RM Reitan","year":"1985","unstructured":"Reitan, R. M. & Wolfson, D. The Halstead\u2013Reitan Neuropsychological Test Battery: Theory and Clinical Interpretation (Neuropsychology Press, 1985)."},{"key":"99794_CR32","volume-title":"Multilingual Aphasia Examination","author":"AL Benton","year":"1978","unstructured":"Benton, A. L. et al. Multilingual Aphasia Examination 3rd edn. (AJA Associates, 1978).","edition":"3"},{"key":"99794_CR33","volume-title":"The Visual Object and Space Perception Battery: VOSP","author":"EK Warrington","year":"1991","unstructured":"Warrington, E. K. & James, M. The Visual Object and Space Perception Battery: VOSP (Pearson, 1991)."},{"issue":"sup1","key":"99794_CR34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/13854046.2019.1574902","volume":"33","author":"BE Kirsebom","year":"2019","unstructured":"Kirsebom, B. E. et al. Demographically adjusted CERAD wordlist test norms in a Norwegian sample from 40 to 80 years. Clin. Neuropsychol. 33(sup1), 27\u201339 (2019).","journal-title":"Clin. Neuropsychol."},{"key":"99794_CR35","volume-title":"Revised Comprehensive Norms for an Expanded Halstead\u2013Reitan Battery: Demographically Adjusted Neuropsychological Norms for African American and Caucasian Adults: Professional Manual","author":"RK Heaton","year":"2004","unstructured":"Heaton, R. K. Revised Comprehensive Norms for an Expanded Halstead\u2013Reitan Battery: Demographically Adjusted Neuropsychological Norms for African American and Caucasian Adults: Professional Manual (Psychological Assessment Resources, 2004)."},{"issue":"2","key":"99794_CR36","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3233\/JAD-180964","volume":"67","author":"E Hessen","year":"2019","unstructured":"Hessen, E. et al. In Brief Neuropsychological Assessment, Amnestic Mild Cognitive Impairment (MCI) Is associated with cerebrospinal fluid biomarkers for cognitive decline in contrast to the prevailing NIA-AA MCI criterion. J. Alzheimers Dis. 67(2), 715\u2013723 (2019).","journal-title":"J. Alzheimers Dis."},{"issue":"4","key":"99794_CR37","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.3233\/JAD-160227","volume":"53","author":"A De Vos","year":"2016","unstructured":"De Vos, A. et al. The cerebrospinal fluid neurogranin\/BACE1 ratio is a potential correlate of cognitive decline in Alzheimer\u2019s disease. J. Alzheimers Dis. 53(4), 1523\u20131538 (2016).","journal-title":"J. Alzheimers Dis."},{"issue":"5","key":"99794_CR38","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","volume":"87","author":"CR Jack Jr","year":"2016","unstructured":"Jack, C. R. Jr. et al. A\/T\/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology 87(5), 539\u2013547 (2016).","journal-title":"Neurology"},{"issue":"1","key":"99794_CR39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s13195-019-0485-0","volume":"11","author":"O Hansson","year":"2019","unstructured":"Hansson, O. et al. Advantages and disadvantages of the use of the CSF amyloid \u03b2 (A\u03b2) 42\/40 ratio in the diagnosis of Alzheimer\u2019s Disease. Alzheimers Res. Ther. 11(1), 34 (2019).","journal-title":"Alzheimers Res. Ther."},{"issue":"10","key":"99794_CR40","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1093\/clinchem\/47.10.1776","volume":"47","author":"M Sjogren","year":"2001","unstructured":"Sjogren, M. et al. Tau and Abeta42 in cerebrospinal fluid from healthy adults 21\u201393 years of age: Establishment of reference values. Clin. Chem. 47(10), 1776\u20131781 (2001).","journal-title":"Clin. Chem."},{"issue":"4","key":"99794_CR41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr","year":"2018","unstructured":"Jack, C. R. Jr. et al. NIA-AA research framework: Toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement. 14(4), 535\u2013562 (2018).","journal-title":"Alzheimers Dement."},{"key":"99794_CR42","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.jad.2019.03.042","volume":"250","author":"A Jamieson","year":"2019","unstructured":"Jamieson, A. et al. Depression related cerebral pathology and its relationship with cognitive functioning: A systematic review. J. Affect. Disord. 250, 410\u2013418 (2019).","journal-title":"J. Affect. Disord."},{"issue":"2","key":"99794_CR43","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1017\/S1041610217001880","volume":"30","author":"Z Ismail","year":"2018","unstructured":"Ismail, Z. et al. Affective and emotional dysregulation as pre-dementia risk markers: Exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria. Int. Psychogeriatr. 30(2), 185\u2013196 (2018).","journal-title":"Int. Psychogeriatr."},{"key":"99794_CR44","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jad.2020.05.020","volume":"274","author":"JK Kuring","year":"2020","unstructured":"Kuring, J. K., Mathias, J. L. & Ward, L. Risk of dementia in persons who have previously experienced clinically-significant depression, anxiety, or PTSD: A systematic review and meta-analysis. J. Affect. Disord. 274, 247\u2013261 (2020).","journal-title":"J. Affect. Disord."},{"issue":"2","key":"99794_CR45","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/acps.12352","volume":"131","author":"E Auning","year":"2015","unstructured":"Auning, E. et al. Neurobiological correlates of depressive symptoms in people with subjective and mild cognitive impairment. Acta Psychiatr. Scand. 131(2), 139\u2013147 (2015).","journal-title":"Acta Psychiatr. Scand."},{"issue":"5","key":"99794_CR46","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1176\/appi.ajp.2011.11081153","volume":"169","author":"N Pomara","year":"2012","unstructured":"Pomara, N. et al. Lower CSF amyloid beta peptides and higher F2-isoprostanes in cognitively intact elderly individuals with major depressive disorder. Am. J. Psychiatry 169(5), 523\u2013530 (2012).","journal-title":"Am. J. Psychiatry"},{"issue":"6627","key":"99794_CR47","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1038\/386824a0","volume":"386","author":"WC Drevets","year":"1997","unstructured":"Drevets, W. C. et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386(6627), 824\u2013827 (1997).","journal-title":"Nature"},{"key":"99794_CR48","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3389\/fphar.2020.00279","volume":"11","author":"C Linnemann","year":"2020","unstructured":"Linnemann, C. & Lang, U. E. Pathways connecting late-life depression and dementia. Front. Pharmacol. 11, 279 (2020).","journal-title":"Front. Pharmacol."},{"issue":"1","key":"99794_CR49","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1038\/s41467-019-09562-7","volume":"10","author":"SE Holmes","year":"2019","unstructured":"Holmes, S. E. et al. Lower synaptic density is associated with depression severity and network alterations. Nat. Commun. 10(1), 1529 (2019).","journal-title":"Nat. Commun."},{"issue":"2","key":"99794_CR50","doi-asserted-by":"crossref","first-page":"e22134","DOI":"10.1002\/syn.22134","volume":"74","author":"X Chen","year":"2020","unstructured":"Chen, X. et al. Synapse impairment associated with enhanced apoptosis in post-traumatic stress disorder. Synapse 74(2), e22134 (2020).","journal-title":"Synapse"},{"issue":"5","key":"99794_CR51","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1001\/archpsyc.65.5.542","volume":"65","author":"X Sun","year":"2008","unstructured":"Sun, X. et al. Amyloid-associated depression: A prodromal depression of Alzheimer disease?. Arch. Gen. Psychiatry 65(5), 542\u2013550 (2008).","journal-title":"Arch. Gen. Psychiatry"},{"issue":"7","key":"99794_CR52","first-page":"333","volume":"37","author":"HJ Weitbrecht","year":"1969","unstructured":"Weitbrecht, H. J. Causes of psychiatric diagnostic errors. Fortschr. Neurol. Psychiatr. Grenzgeb 37(7), 333\u2013349 (1969).","journal-title":"Fortschr. Neurol. Psychiatr. Grenzgeb"},{"key":"99794_CR53","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jns.2019.04.019","volume":"402","author":"S Salimi","year":"2019","unstructured":"Salimi, S. et al. Visuospatial dysfunction in Alzheimer\u2019s disease and behavioural variant frontotemporal dementia. J. Neurol. Sci. 402, 74\u201380 (2019).","journal-title":"J. Neurol. Sci."},{"key":"99794_CR54","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1111\/ene.14658","volume":"28","author":"I \u00c1lvarez","year":"2020","unstructured":"\u00c1lvarez, I. et al. Added value of cerebrospinal fluid multimarker analysis in diagnosis and progression of dementia. Eur. J. Neurol. 28, 1142\u20131152 (2020).","journal-title":"Eur. J. Neurol."},{"key":"99794_CR55","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.trci.2018.10.003","volume":"4","author":"BE Kirsebom","year":"2018","unstructured":"Kirsebom, B. E. et al. Cerebrospinal fluid neurogranin\/beta-site APP-cleaving enzyme 1 predicts cognitive decline in preclinical Alzheimer\u2019s disease. Alzheimers Dement. 4, 617\u2013627 (2018).","journal-title":"Alzheimers Dement."},{"issue":"1","key":"99794_CR56","first-page":"e12027","volume":"12","author":"H Brodaty","year":"2020","unstructured":"Brodaty, H. & Connors, M. H. Pseudodementia, pseudo-pseudodementia, and pseudodepression. Alzheimers Dement. 12(1), e12027 (2020).","journal-title":"Alzheimers Dement."},{"issue":"3","key":"99794_CR57","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/brain\/awy347","volume":"142","author":"JC Park","year":"2019","unstructured":"Park, J. C. et al. Plasma tau\/amyloid-\u03b21-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer\u2019s disease. Brain 142(3), 771\u2013786 (2019).","journal-title":"Brain"}],"updated-by":[{"DOI":"10.1038\/s41598-022-22274-1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,10,18]],"date-time":"2022-10-18T00:00:00Z","timestamp":1666051200000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-99794-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-99794-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-99794-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T16:47:42Z","timestamp":1670086062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-99794-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,13]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["99794"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-99794-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,13]]},"assertion":[{"value":"6 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 October 2022","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41598-022-22274-1","URL":"https:\/\/doi.org\/10.1038\/s41598-022-22274-1","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20375"}}