Published: 13-03-2024 11:31 | Updated: 13-03-2024 17:31

New study links DEK protein to Alzheimer’s neuronal vulnerability

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A new study from Karolinska Institutet, published in Brain, reveals a connection between the protein DEK and early neuronal changes in Alzheimer’s disease. Researchers found that lower DEK levels in vulnerable neurons lead to altered neuronal activity and Tau protein accumulation, offering insights into early-stage Alzheimer’s pathology and potential therapeutic targets.

Patricia Rodriguez Rodriguez. Photo: Yingyu Tang

What does your publication show?

”We study neurons that are especially vulnerable to Alzheimer’s disease, as they degenerate very early on in the disease progression. In these neurons, we show that lower levels of the protein DEK, with previously unknown function, leads to alterations in neuronal activity and to the accumulation of the protein Tau, that is characteristic of Alzheimer’s Disease pathology. This effect is accompanied by the reactivity of immune cells in the brain and by the loss of these neurons” says corresponding author Patricia Rodriguez Rodriguez, Senior Research Specialist at the Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society.

Why are the results important?

”In Alzheimer’s Disease, some groups of neurons within specific brain regions degenerate years before the patients develop symptoms. The reasons for the vulnerability of these neurons are unknown and could hold the key for the development of therapies aimed at treating the disease at its earliest stages, when they could be more effective.
The current study identifies a novel player that triggers pathological alterations in these neurons, and sheds light into the pathways that contribute to the early neurodegeneration in Alzheimer’s disease”.

How did you perform the study?

”In collaboration with leading computational genomics experts  from Rice University and with the co-corresponding author Dr. Jean Pierre Roussarie (Boston University), we used a novel, computer-based method to predict Alzheimer’s disease drivers (Neuron, 2020). This method helped us to identify, in a fully data-driven manner, the protein DEK as a potential driver of AD pathology. Considering that its function in the brain was unknown, we modulated its levels in Alzheimer’s vulnerable neurons both in mouse models and cells in culture. This helped us to study how its gain or loss of function affects the biology of these neurons and whether it triggered pathological alterations”.

What is the next step in your research?

”We will focus on understanding how DEK function is affected by different AD drivers and risk factors, and whether the modulation of this protein and/or its related pathways can prevent disease progression. We will also explore how a genetic mutation in its gene affects its function and its effect on disease onset and progression on the population that carries it”.


A cell autonomous regulator of neuronal excitability modulates tau in Alzheimer's disease vulnerable neurons.
Rodriguez-Rodriguez P, Arroyo-Garcia LE, Tsagkogianni C, Li L, Wang W, Végvári Á, Salas-Allende I, Plautz Z, Cedazo-Minguez A, Sinha SC, Troyanskaya O, Flajolet M, Yao V, Roussarie JP, Brain, online March 11, 2024.