{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:33:15Z","timestamp":1789936395420,"version":"4.0.1"},"reference-count":59,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T00:00:00Z","timestamp":1475193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004963","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["FP7\/2007\u20102013"],"award-info":[{"award-number":["FP7\/2007\u20102013"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006603","name":"Bundesministerium f\u00fcr Bildung und Frauen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006603","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. The objective of this study was to investigate the relationships between cerebral amyloid production and both blood and cerebrospinal fluid (CSF) markers of the homocysteine metabolism. We assessed CSF concentrations of soluble APP\u03b1, soluble APP\u03b2, and amyloid \u03b21\u201042 (A\u03b21\u201042), as well as plasma levels of homocysteine (Hcys), total vitamin B12, and folate, and CSF concentrations of homocysteine (Hcys\u2010CSF), 5\u2010methyltetrahydrofolate (5\u2010MTHF), S\u2010adenosylmethionine (SAM), and S\u2010adenosylhomocysteine (SAH) in 59 subjects with normal cognition. Linear regression analyses were performed to assess associations between homocysteine metabolism parameters and amyloid production. The study was approved by the Ethical Committee of the University of Bonn. After controlling for age, gender, APOEe4 status, and albumin ratio (Qalb), higher A\u03b21\u201042 CSF levels were associated with high Hcys and low vitamin B12 plasma levels as well as with high Hcys, high SAH, and low 5\u2010MTHF CSF levels. Higher CSF concentrations of sAPP\u03b1 and sAPP\u03b2 were associated with high SAH levels. The results suggest that disturbed homocysteine metabolism is related to increased CSF levels of sAPP forms and A\u03b21\u201042, and may contribute to the accumulation of amyloid pathology in the brain.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13766-fig-0003-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nDisturbed homocysteine metabolism may contribute to amyloidogenesis by modulating the amyloid precursor protein (APP) production and processing. We found associations between CSF levels of soluble APP forms and A\u03b21\u201042, and markers of the homocysteine metabolism in both plasma and CSF in adults with normal cognition. Disturbed homocysteine metabolism may represent a target for preventive and early disease\u2010modifying interventions in Alzheimer's disease.\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13766","type":"journal-article","created":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T09:02:41Z","timestamp":1470819761000},"page":"324-332","source":"Crossref","is-referenced-by-count":35,"title":["Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta"],"prefix":"10.1111","volume":"139","author":[{"given":"Aikaterini","family":"Oikonomidi","sequence":"first","affiliation":[{"name":"Department of Psychiatry Division of Old Age Psychiatry University Hospital of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Lewczuk","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University of Erlangen Erlangen Germany"},{"name":"Department of Neurodegeneration Diagnostics Medical University of Bialystok Bialystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kornhuber","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University of Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvo","family":"Smulders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine VU University Medical Centre Amsterdam The Netherlands"},{"name":"Institute \u00a0for \u00a0Cardiovascular \u00a0Research \u00a0ICaR\u2010VU VU \u00a0University \u00a0Medical \u00a0Centre \u00a0Amsterdam \u00a0The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Linnebank","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Semmler","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Popp","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Division of Old Age Psychiatry University Hospital of Lausanne Lausanne Switzerland"},{"name":"Department of Psychiatry and Psychotherapy University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2009.02212.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"751","DOI":"10.3233\/JAD-2012-112138","article-title":"Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease","volume":"31","author":"Arlt S.","year":"2012","journal-title":"J. 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