Miren Altuna Azkargorta, a predoctoral researcher at Navarrabiomed’s Neuroepigenetics Unit, will defend her doctoral dissertation for the Universidad Pública de Navarra on Thursday, January 14. The defense will take place via videoconference and with limited attendance at 12 noon in the Navarrabiomed assembly hall (only people with prior authorization are permitted to attend the event in person). While preparing her dissertation, “Identification of epigenetic biomarkers in Alzheimer’s disease,” Miren Altuna was supervised by Maite Mendioroz Iriarte, a Navarrabiomed researcher and neurologist at the Hospital Complex of Navarre, and CHN internist Gregorio Tiberio López, her dissertation advisor.

Alzheimer’s disease (AD) is a neurodegenerative disease and the most common cause of dementia. In the last few decades, its prevalence has increased as a result of the aging population. AD is a multifactorial disease in that both genetic and environmental risk factors contribute to the disorder, although its pathogenesis is not yet fully understood. The study of epigenetics therefore plays a key role. Epigenetic mechanisms, which are partially inherited but can also be altered by environmental factors, modify gene expression without changing the DNA sequence.

The work of Miren Altuna aims to identify a footprint of DNA methylation (the most widely studied epigenetic mechanism) typical of AD by using the human hippocampus, an area of the brain that is particularly affected by the pathogenic mechanisms of AD. To achieve this, different strategies were used: (1) The study of DNA methylation changes by means of the genome-wide strategy, and (2) The study of changes in the methylation pattern for a given gene, in this case the PLD3 gene (it has previously been reported that a polymorphism of this gene increases the risk of developing AD).

The findings included identification of a differentially methylated pattern affecting the genes involved in neurogenesis in the hippocampus and differential methylation of the alternative promoter region of the candidate gene PLD3. It has been hypothesized that changes in DNA methylation could contribute to alterations in the regulation of neurogenesis previously described in the hippocampus of subjects with AD and that the risk conferred by the PLD3 gene in the development of AD may be related to changes in its epigenetic regulation.

The results presented support the existence of a specific epigenetic footprint of AD that could potentially be useful as a source of diagnostic and/or prognostic biomarkers and could therefore lead to progress in the knowledge of the pathogenesis of AD and the potential identification of future therapeutic targets. These findings have been published in three articles in indexed journals: Clinical Epigenetics (https://doi.org/10.1186/s13148-019-0672-7 and https://doi.org/10.1186/s13148-018-0547-3) and Neurología.

Miren Altuna also made her doctoral work public at the 2017 and 2019 international congresses of the European Academy of Neurology and at the 69th annual meeting of the Spanish Society of Neurology in 2017.