EARLY SIGNS OF NEUROINFLAMMATION AND VASCULAR DYSFUNCTION IN EXPERIMENTAL ALZHEIMER´S DISEASE. IS THE HILUS PARTICULARLY SUSCEPTIBLE?

SARAVIA F

Cairns

Congreso; Meeting International Society for Neurochemistry; 2015

ISN

Alzheimer's disease (AD) is a progressive neurodegenerative disorder without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. We studied early alterations of hippocampal glia and microvasculature besides their progression during the neuropathology in PDAPP-J20 transgenic mice, recognized AD model. At 3 m, before deposits formation but assessable levels of soluble Aβ1-40 and 1-42, microglial Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus of the dentate gyrus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onwards selectively in the hilus, in coincidence with prominent amyloid Congo red + deposition. The microvasculature is also affected in AD showing morphological aberrations in the hippocampus. At pre-plaque stages we detected a decreased presence of the tight junction protein occludin in the hilus, suggestive of premature brain blood barrier disruption. Our work emphasizes the role of brain vessels and glia- as key constituents of the neurovascular unit- from the onset of the disease in an AD transgenic mice and focuses on a hippocampal subfield that revealed a special vulnerability as well as seems to be early implicated