Descripción del proyecto
Una mirada sin precedentes a la patología de la enfermedad de Alzheimer temprana
La enfermedad de Alzheimer (EA) es un trastorno neurológico progresivo y la causa más común de demencia. Los mecanismos moleculares tempranos de la EA apenas son conocidos debido a la falta de muestras de tejidos humanos representativos de las etapas iniciales de la enfermedad. Se cree que la microglía, formada por células especializadas del cerebro, desempeñan un papel esencial en la disfunción neurológica y el declive cognitivo. El innovador proyecto HUMANE, financiado con fondos europeos, investigará esta cuestión en la EA temprana mediante una muestra única de tejido cerebral de ciertos pacientes que presentan la patología temprana de la EA como parte de otra afección. Los resultados podrían indicar el camino de posibles dianas terapéuticas y biomarcadores de la EA.
Objetivo
The molecular mechanisms leading to Alzheimer's disease (AD) are poorly understood. This is due to lack of human tissue samples for research representing early changes of AD pathology. The accumulating pathology, including beta-amyloid and tau proteins, are manifested by concomitant neuroinflammatory reactions geared by malfunctional microglia. Microglia in the human and mouse AD brain exist in various subpopulations from which a specific, disease-associated microglia population is thought to be involved in AD pathogenesis. However, there is no evidence on whether and how these specific microglial subpopulations actually impair neuronal functions in human AD brain. I will now assess neuron-glia network activities and functions indicative of early AD pathology in humans. I hypothesize that early AD pathology selectively impairs neuronal circuits and that glial cells, especially specific microglia subpopulations, contribute to neuronal dysfunction and cognitive decline. These events contribute to a detectable vesicle-based biomarker profile in cerebrospinal fluid and blood prior the clinical disease. Due to early AD pathology present in a subpopulation of idiopathic normal pressure hydrocephalus (iNPH) patients, the brains of the iNPH patients offer a unique window to evaluate cellular and molecular events occurring during early AD. I combine a series of state-of-the art techniques to answer how and what glial cell subpopulations are associated with altered neuronal network activities at subcellular and spatial resolution in human brain impacted by early AD-related pathology. Novel methodologies established in my lab, knowhow and access to unique brain samples make me uniquely positioned to form a holistic view on how early AD-pathology impacts cellular functions at multiple levels. This will pinpoint novel molecular targets for further validation and new fluid biomarkers.
Ámbito científico
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencescell biology
- medical and health sciencesbasic medicinepathology
- natural sciencesbiological sciencesmolecular biologymolecular neuroscience
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-ERC - HORIZON ERC GrantsInstitución de acogida
70211 KUOPIO
Finlandia