Alzheimer's disease and other dementias

Alzheimer's disease (AD) is a highly disabling neurodegenerative disease and the leading cause of dementia. It currently affects 3.5 million people in Europe, 400,000 of them in Spain and due to the increase in life expectancy, the incidence of the disease is expected to double in the coming years. This fact, together with the lack of effective treatments capable of slowing down the progression of the disease, makes it necessary to investigate the development of new effective therapies.

Our objective is to study the pathophysiological bases of cognitive decline in AD in order to identify new therapeutic targets and to develop pharmacological or gene therapy treatments capable of delay or stop the progression of the disease. For this aim, we used transgenic mice that overexpress the proteins that constitute the histopathological markers of AD (beta amyloid and tau). The onset and progression of these histopathological markers, as well as their functional and structural impact, are studied through the analysis of molecular and histological markers, measures of synaptic connectivity and behavioral tests. The determination of these parameters are used to monitor the progression of the disease and allow  assessing the effects that the new treatments have on the memory and learning capacity of the animals.

Currently our main projects are:

  • Search for factors responsible for resilience to AD as new therapeutic targets

    Several studies have shown that there are individuals with the characteristic histopathological lesions of the Alzheimer's brain but 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 disorders (resilient mice) will be studied and compared to classical impaired age-matched Tg2576 mice. The identification of 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.

    IP: Ana García-Osta, Mar Cuadrado-Tejedor

  • Development of new experimental models that reproduce the pathogenesis observed in patients

    It is necessary to develop animal models of AD that recapitulate more reliably the human pathology. In this project, the use of an adeno-associated virus that expresses the human Tau protein with the P301L mutation (AAV-hTauP301L) will be used to   generate Tau pathology in a context of amyloid pathology. This model will serve to study the cross-talk of these proteins in the development of the pahtology, as well as to test more accurately new AD treatments.

    IP: Ana García-Osta, Mar Cuadrado-Tejedor

  • Search for clinical biomarkers of the disease: imaging and liquid biopsy

    The objective is to identify new biomarkers of Alzheimer's disease that allow its diagnosis in the symptomatic and prodromal phase and the monitoring of its progression. For them, we combine brain PET studies to evaluate β-amyloid and tau deposits and brain metabolism, structural and functional magnetic resonance imaging, analysis of markers in cerebrospinal fluid and plasma, where we carried out studies of circulating microRNAs (miRNAs) and contained in exosomes.

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

More information:

Contact

Contact:
Cristina Canciani
Avda. Pío XII, 55
31008 Pamplona
Spain

(+34) 948 194 700 Ext. 2013
canciani@unav.es