Hippocampal level of LSD1 correlates with intracellular amyloid-beta

BISTUÉ MILLÓN, M. BEATRIZ; GODOY, MARTIN SERGIO; BRUNO, MARTIN ALEJANDRO

Los Angels

Conferencia; AAIC; 2019

Alzheimer Association USA

Background: Lysine-specific demethylase 1 (LSD1) function as a transcriptional repressor or activator by demethylation of histone H3 on lysine 4 or 9 and regulates different physiological processes including inflammatory responses and learning and memory. In the present study, we investigate chronological hippocampal levels of LSD1 and its correlation with the expression of pro-inflammatory markers, analyzing simultaneously β-amyloid levels and cognitive performance of our transgenic AD-like rats. Methods: We used the hemizygous McGill-R-Thy1-APP transgenic rats, which progressively accumulates intraneuronal Aβ peptide and display cognitive deficits (Leon, et al. 2010). Posterior to cognitive status test assessed by Morris water maze, hippocampal β-amyloid accumulation, LSD1 levels and inflammatory protein markers expression were measured by western blot at different ages (3, 6, 12 and 18 months old) of non-transgenic (APP-/-) and hemizygous (APP+/-) transgenic rats. Results: Increased levels of LSD1 at very early stages of the amyloid pathology (6 months old) in hippocampus of APP+/- transgenic rats displayed a positive correlation through age during the progression of Aβ pathology (Pearson r2=0.77 (6 months); 0.87 (12 months) and 0.82 (18 months), respectively p