MICROGLIAL ALTERATIONS BEFORE AND AFTER PLAQUE DEPOSITION IN PDAPP-J20 MICE, MODEL OF ALZHEIMER'S DISEASE.

PAVÍA P; VINUESA A; POMILIO C; BEAUQUIS J; SARAVIA F

Huerta Grande , Córdoba

Congreso; Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2014

Alzheimer´s disease (AD) is a progressive neurodegenerative disease without effective therapy and the principal cause of dementia. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell changes and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal microglia and their progression during the pathology in PDAPP-J20 transgenic mice, carrying human APP gene with Swe and Ind mutations, at 3, 9 and 15 months (m) of age. Age-matched non transgenic mice were used as controls. At 3 m, before plaque formation, Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus (42.16 ± 5.95 µm2 vs 34.54 ± 2.01 µm2, p less than 0.05), whereas these alterations appeared 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 deposition, evidenced by Congo Red staining. At advanced stages, microglial cells seem to be intimately involved in amyloid degradation. Colocalization of Iba1 with ubiquitin or p62 was exclusively found in cells contacting deposits in AD mice from 9 m onwards. Our work emphasizes the role of glia in AD onset and focuses on a brain subfield revealed as especially susceptible in this disease.