Alzheimer's Disease

"We are looking for biomarkers of resilience or resistance to developing the disease to identify new therapeutic targets."

DR. ANA Mª GARCÍA OSTA
RESEARCHER. ALZHEIMER'S DISEASE RESEARCH GROUP

Alzheimer's disease is the most common neurodegenerative pathology and the main cause of dementia, a highly disabling brain disorder.

It currently affects 3.5 million people in Europe, 400,000 of them in Spain. The incidence of this disease is expected to double in the coming years due to the increase in life expectancy.

There is no treatment capable of slowing the progression of the disease, so research is needed to develop new effective therapies.

In the Alzheimer's Disease Group at Cima, we study in depth the physical and chemical processes that cause this disease in order to identify new therapeutic targets and develop pharmacological or gene therapy treatments to slow down or stop the progression of the disease.

To do this, we use transgenic mice that overexpress the proteins that constitute the histopathological markers of Alzheimer's disease (beta amyloid and tau). The onset and progression of these histopathological markers, as well as their functional and structural impact are studied by analyzing molecular and histological markers, synaptic connectivity measurements and behavioral tests. All these parameters together allow us to quantify the progression of the disease and to assess the effects of new treatments on the memory and learning ability of the animals.

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Alzheimer's Disease
Research Group Objectives

Study of the pathophysiological basis of cognitive impairment in Alzheimer's disease.

Identify new disease biomarkers and potential therapeutic targets.

Develop drug treatments or gene therapy to slow or halt disease progression.

Resilience in Alzheimer's disease

MOLECULAR MECHANISMS

Alzheimer's Disease Laboratory

As in humans, approximately 20% of animal models with Alzheimer's disease retain their ability to learn despite having severe pathology in their brains.

Our group has identified a new possible therapeutic target for Alzheimer's disease: the PLA2G4E protein that could make us "resilient" to present this disease.

Elevated levels of this enzyme point to it as a protective factor in the prevention of memory loss associated with Alzheimer's disease.

Lines of research

PI: Ana García-Osta, Mar Cuadrado-Tejedor

Objectives:

Several studies have shown that there are individuals with histopathological lesions characteristic of Alzheimer's brain which do not develop dementia.

In this project, the objective is to decipher the factors responsible for this resilience. To develop this project, mice of the Tg2576 line that do not develop cognitive alterations (resilient mice) will be studied. In this line, our group has identified a new potential therapeutic target for Alzheimer's disease: the PLA2G4E protein that could make us "resilient" to Alzheimer's disease.

Identifying these factors could help to understand the pathogenesis of AD and facilitate the identification of new therapeutic targets for the prevention or treatment of the disease.

Learn more about the project in our Pipeline.

PI: Ana García-Osta, Mar Cuadrado-Tejedor

Objectives:

There is a need for the development of animal models of AD that more reliably recapitulate human pathology.

This project proposes the use of an adenoassociated virus expressing human Tau protein with the P301L mutation (AAV-hTauP301L), to try to generate Tau pathology in a context of amyloid pathology.

This model will serve to study how both proteins interact in the development of pathological markers and neuronal death, as well as to test more precisely new treatments in development.

PI: Mario Riverol, Marta Fernandez-Matarrubia, Rosario Luquin, Alberto Perez-Mediavilla

Objectives:

To identify surrogate markers of Alzheimer's disease that allow its diagnosis in symptomatic and prodromal phase and the monitoring of its progression.

For this purpose, we combine brain PET studies to evaluate β-amyloid and tau deposits and brain metabolism, structural and functional MRI, analysis of markers in cerebrospinal fluid and plasma, where we carry out studies of circulating microRNAs (miRNAs) and exosome contents.