BDNF Val66Met Genotype, DNA Methylation, mRNA, and Protein Levels as Potential Blood-Based Biomarkers for Dementia and Cognitive Decline

Tudor, Lucija; Videtič Paska, Alja; Konjevod, Marcela; Balić, Nikola; Nikolac Perković, Matea; Uzun, Suzana; Vuić, Barbara; Miloš, Tina; Nedić Erjavec, Gordana; Mimica, Ninoslav; Kouter, Katarina; Pivac, Nela; Švob Štrac, Dubravka (2025) BDNF Val66Met Genotype, DNA Methylation, mRNA, and Protein Levels as Potential Blood-Based Biomarkers for Dementia and Cognitive Decline. International Journal of Molecular Sciences, 26 (18). ISSN 1422-0067

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	BDNF; Val66Met polymorphism; DNA methylation; gene and protein expression; dementia; MCI
Subjects:	NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Neuroscience BIOMEDICINE AND HEALTHCARE > Clinical Medical Sciences > Psychiatry
Divisions:	Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type Terapijski potencijal neurosteroida i neurotrofina u demenciji-TePoNeDe Dubravka Švob Štrac; Ninoslav Mimica; Suzana Uzun; Oliver Kozumplik; Julija Erhardt; Ana-Marija Domijan; Dora Zelena; Erika Pinter; Coral Barbas IP-2019-04-6100 HRZZ
Depositing User:	Kristina Ciglar
Date Deposited:	26 Nov 2025 12:11
URI:	http://fulir.irb.hr/id/eprint/10239
DOI:	10.3390/ijms26188987

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