Role of microglia in Alzheimer´s disease: Benefits of its modulation
Laboratory of Neurobiology (Achucarro)
Alzheimer´s disease (AD) is the most prevalent form of dementia in elderly people and is characterized by neurodegeneration with irreversible memory loss. The most widely accepted pathophysiological model of the disease is supported by the "amyloid hypothesis" which proposes that the amyloid-β (Aβ) peptide is responsible for cognitive impairment and actively contribute to the development of the disease. Neuroinflammation is also a key contributor to AD and plays a central role in its pathogenesis.Despite the capacity of microglia, immune cells of the central nervous system, to clear some Aβ species in vitro, the accumulation of Aβ guides the progression of the disease. In AD and AD models, microglia, is concentrated around Aβ plaques but seems to have little capacity to eliminate Aβ, and plaques stay for long time in the brain. Moreover, it has been also reported that microglia mediates early synapse loss in AD models. In contrast, activation of microglia by immunotherapy or with some cytokines results in a more efficient Aβ degradation and the recovery of synapses. Thus, the main goal of our research is to better understand the role of microglia in AD and to find compounds that boost its beneficial functions. Our projects have two main objectives: 1) to study microglia-neuron interaction on AD models and, 2) to analyze microglia modulation as therapeutic target for AD. We used primary co-cultures, ex vivo and in vivo AD models to address proposed objectives. I will summarize our main recent results from the ongoing projects. Further understanding the role of microglia in AD is necessary for the development of more efficient strategies against AD.
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