Dementia prevention

The DNA as a musical score and the key of epigenetics to understand Alzheimer's

Study coordinated by Sapienza University of Rome reveals a dialogue between two mechanisms of gene regulation, paving the way for the possibility of controlling 'upstream' amyloid plaque formation

by Andrea Fuso *

20 October 2025

3' min read

Translated by AI

Versione italiana

3' min read

Translated by AI

Versione italiana

In recent years, the term 'epigenetics' has become very fashionable, from nutrition to cosmetics to the humanities. A media success that, however, risks losing its authentic and scientific meaning.

The DNA as a piece of music

To understand this, let us imagine our DNA as a piece of music: the notes are all there, written in sequence, but what makes the difference is the arrangement and the tone with which they are played. Epigenetics represents just that: the combination of certain specific chemical modifications of the DNA and the proteins in the cell nucleus, deciding how intensively a gene should be 'performed', i.e. translated into a protein.

All our cells possess the same genes, yet they do not express them in the same way: a liver cell 'plays' different genes than a neuron, despite having the same genetic score. This happens thanks to epigenetic mechanisms, which allow the cell to express the right gene at the right time.

But there is a crucial aspect, these mechanisms can be altered by external environmental stimuli such as nutrients, pollutants, chronic stress. When this happens, pathological molecular processes can be triggered, paving the way for disease.

The complexity of Alzheimer's

Alzheimer's disease, with its baggage of multiple risk factors, appears to have a clear epigenetic component. The multifactorial nature of the cause is reflected at the molecular level: in the brains of Alzheimer's patients, we observe alterations in several processes simultaneously, from the accumulation of amyloid and tau proteins to chronic neuroinflammation, from oxidative stress to mitochondria malfunction and deterioration of the blood-brain barrier.

It is precisely this complexity that makes the study of Alzheimer's so challenging. An effective cure, which unfortunately does not exist at the moment, will not have to act on a single target, but coordinate interventions on all these mechanisms simultaneously.

And this is where epigenetics becomes really interesting. Epigenetic factors seem to be able to coordinate many of these molecular mechanisms and, above all, are potentially reversible. Unlike permanent genetic mutations, epigenetic modifications can be corrected, opening up concrete prospects for intervention.

The study on "Alzheimer's & Dementia"

In our laboratory, at the Department of Experimental Medicine at La Sapienza in Rome, we have been studying an epigenetic factor, DNA methylation, in relation to amyloid production in models of Alzheimer's for over 20 years. Initial results revealed how a deficiency in B vitamins increases the activity of two crucial genes (PSEN1 and BACE1), while supplementation with S-adenosylmethionine (the molecule that supplies methyl) counteracts these effects. For PSEN1 the mechanism was clear from the outset: DNA methylation directly regulates it. But for BACE1 the link remained hidden, until today.

In the study recently published in 'Alzheimer's & Dementia', the official journal of the Alzheimer's Association, we have finally clarified the mechanism. BACE1 is regulated by microRNA-29a, which in turn is controlled by DNA methylation. A cascade in which two epigenetic mechanisms (methylation and microRNA) talk to each other to control amyloid production.

These results clarify the cause-effect connection between epigenetics and Alzheimer's, suggest the use of epigenetic markers for early diagnosis and open up concrete perspectives towards therapeutic interventions.

We are now awaiting with interest the results of the first clinical trial of S-adenosylmethionine underway in Australia. In the meantime, we are evaluating combinations with other interventions such as vitamin K and 'stamina' (a fish oocyte extract) for a 'multi-target' therapeutic approach.

The study was co-ordinated by the Department of Experimental Medicine and the 'D. Bovet' Centre for Neuroscience Research (CRiN) of La Sapienza University of Rome, in collaboration with the Universities of Naples 'Federico II' and Barcelona.

* Associate Professor of Clinical Biochemistry and Clinical Molecular Biology - Dept. of Experimental Medicine - Sapienza University of Rome"