{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T16:30:44Z","timestamp":1783528244494,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Croatian Science Foundation","award":["IP-2019-04-6100"],"award-info":[{"award-number":["IP-2019-04-6100"]}]},{"name":"Croatian Ministry of Science and Education, Croatian-Slovenian bilateral project","award":["IP-2019-04-6100"],"award-info":[{"award-number":["IP-2019-04-6100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain-derived neurotrophic factor (BDNF) plays a crucial role in cognitive functions and dementia. In individuals with mild cognitive impairment (MCI) and dementia, we have investigated BDNF Val66Met genotype distribution, peripheral BDNF DNA methylation, mRNA and protein levels, and cognitive performance using the Mini-Mental State Examination (MMSE) and Clock Drawing Test (CDT). Lower BDNF_IV1 methylation had predictive value for dementia. Patients with mild-to-moderate dementia had lower levels of BDNF_IV2 methylation, whereas patients with severe dementia had higher levels than the MCI group, while BDNF_IV2 methylation positively correlated with CDT scores. An insignificant decline in BDNF mRNA levels in dementia patients positively correlated with significantly lower BDNF plasma levels, especially pronounced in severe dementia patients. BDNF mRNA and protein levels were positively correlated with CDT and MMSE scores, respectively. BDNF Val66Met polymorphism was associated with methylation of the BDNF_IX amplicon, but not with methylation in BDNF promoters I and IV, peripheral BDNF gene and protein expression, MMSE and CDT scores, or dementia. Methylation at the BDNF Val66Met site was positively correlated with overall BDNF_IX methylation and methylation at 5 BDNF_IX CpG loci but negatively correlated with methylation of BDNF_IV1, BDNF_IV3, and BDNF_I1 amplicons. Further studies should evaluate the translational potential of these peripheral BDNF-based biomarkers for dementia.<\/jats:p>","DOI":"10.3390\/ijms26188987","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:56:46Z","timestamp":1758013006000},"page":"8987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["BDNF Val66Met Genotype, DNA Methylation, mRNA, and Protein Levels as Potential Blood-Based Biomarkers for Dementia and Cognitive Decline"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9125-406X","authenticated-orcid":false,"given":"Lucija","family":"Tudor","sequence":"first","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-5417","authenticated-orcid":false,"given":"Alja","family":"Videtic Paska","sequence":"additional","affiliation":[{"name":"Centre for Functional Genomics and Biochips, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Konjevod","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2627-3832","authenticated-orcid":false,"given":"Nikola","family":"Balic","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3113-0778","authenticated-orcid":false,"given":"Matea","family":"Nikolac Perkovic","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department for Biological Psychiatry and Psychogeriatry, University Psychiatric Hospital Vrapce, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Vuic","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, 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Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-959X","authenticated-orcid":false,"given":"Katarina","family":"Kouter","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nela","family":"Pivac","sequence":"additional","affiliation":[{"name":"University of Applied Sciences Hrvatsko Zagorje Krapina, 49000 Krapina, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6200-2405","authenticated-orcid":false,"given":"Dubravka","family":"Svob Strac","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, 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