Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer's disease - PubMed (original) (raw)

Glucocorticoids enhance Aβ production in a time- and concentration-dependent manner. N2A cells were incubated with dexamethasone (100 n

to 10 μ

; n = 3 per condition) (a) or corticosterone (100 n

to 10 μ

; n = 3 per condition) (b) for 24–72 h, and Aβ levels were measured from cell media by sandwich ELISA. Aβ42 levels were expressed as a percentage of control Aβ40, shown in the thatched area. *p < 0.05, significance versus controls for either Aβ40 or Aβ42. Control Aβ40 levels average out at ∼1 pg of Aβ40 microgram of protein for a 24 h period into 1 ml of media. c, N2A cells were incubated for 72 h with or without mifepristone (Mif; 10 μ

; n = 3) or spironolactone (Spiro; 100 n

; n = 3) and in the presence or absence of 1 μ

dexamethasone (Dex; n = 3 per condition), and media Aβ levels were measured. *p < 0.05, significance versus controls for either Aβ40 or Aβ42. d, Treatment of N2A cells with dexamethasone (Dex; 1 μ

, 48 h; n = 3) or corticosterone (Cort; 5 μ

, 48 h; n = 3) or control (Con; 48 h; n = 3) increases steady-state levels of full-length APP and selectively increases in C99 as shown by Western blot. e, Quantification of d with protein levels normalized to β-actin levels as a loading control. *p < 0.05, significance versus controls. f, mRNA levels of mouse APP and BACE are increased after 72 h treatment with 10 μ

dexamethasone, as measured by real-time PCR. *p < 0.05, significance versus controls. g, Pulse chase analyses of 35S-labeled APP after treatment of N2A cells with 10 μ

dexamethasone for 72 h (D; n = 3) or control (C; n = 3). Cells were pulsed with 35S, after starvation, for 1 h and chased at the 0, 1, 4, and 8 h time points.