Difference in Methylation and Expression of Brain-Derived Neurotrophic Factor in Alzheimer’s Disease and Mild Cognitive Impairment

Author:

Kouter Katarina1ORCID,Nikolac Perkovic Matea2ORCID,Nedic Erjavec Gordana2ORCID,Milos Tina2,Tudor Lucija2ORCID,Uzun Suzana34,Mimica Ninoslav34ORCID,Pivac Nela2,Videtic Paska Alja1ORCID

Affiliation:

1. Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia

2. Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia

3. Department for Biological Psychiatry and Psychogeriatrics, University Psychiatric Hospital Vrapce, 10090 Zagreb, Croatia

4. School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

Abstract

Due to the increasing number of progressive dementias in the population, numerous studies are being conducted that seek to determine risk factors, biomarkers and pathological mechanisms that could help to differentiate between normal symptoms of aging, mild cognitive impairment (MCI) and dementia. The aim of this study was to investigate the possible association of levels of BDNF and COMT gene expression and methylation in peripheral blood cells with the development of Alzheimer’s disease (AD). Our results revealed higher expression levels of BDNF (p < 0.001) in MCI subjects compared to individuals diagnosed with AD. However, no difference in COMT gene expression (p = 0.366) was detected. DNA methylation of the CpG islands and other sequences with potential effects on gene expression regulation revealed just one region (BDNF_9) in the BDNF gene (p = 0.078) with marginally lower levels of methylation in the AD compared to MCI subjects. Here, we show that the level of BDNF expression in the periphery is decreased in subjects with AD compared to individuals with MCI. The combined results from the gene expression analysis and DNA methylation analysis point to the potential of BDNF as a marker that could help distinguish between MCI and AD patients.

Funder

Research Programme

Slovenian Research Agency

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

Reference98 articles.

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4. WHO (2016). International Statistical Classification of Diseases and Related Health Problems, World Health Organization. 10th Revision icd-10: Tabular List.

5. Tanaka, M., and Vécsei, L. (2022). Editorial of special issue ‘dissecting neurological and neuropsychiatric diseases: Neurodegeneration and neuroprotection’. Int. J. Mol. Sci., 23.

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