Special Lecture

Microglia and Hypoxia: Implications for Alzheimer's disease

Alberto Pascual, PhD

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. For a long time has been recognized that the progress of AD is producing a concomitant decrease in brain oxygen availability. The main hypotheses to explain brain hypoxia in AD are associated with Aß deposition in the microvasculature (amyloid angiopathy) and the dysfunction of the Locus coeruleus, a brain region suggested as a controller of brain blood flow. In addition, a clear association is observed between vascular pathology and AD. To investigated the ability of sustained hypoxia to modify the progression of an AD mice model, we have challenged the APP(swe)/PS1∆E9 AD model by exposing these animals to physiological hypoxia (8% oxygen, 20 days) at initial (8 months) and late stages (14 months) of the disease. Microglia is affected by hypoxia in an age related way, leading in aged animals to a decrease of the total number of microglia cells and a clear depopulation of Aß plaques, leaving the Aß deposits in direct contact with other brain cells. We have also analyzed the main parameters related with Aß production and estimated the regulation by hypoxia of the expression of different genes related with Aß production/degradation.