HIV-1 Tat contributes to Alzheimer's disease-like pathology in PSAPP mice.

摘要: Prevalence of HIV-associated cognitive impairment is rising. Amyloid-beta (A-beta) plaque deposition in the brain may be a contributing factor as epidemiological data suggests significant numbers long-term HIV survivors are at elevated risk developing Alzheimer's disease (AD). HIV-1 Tat-induced A-beta deposition, tau phosphorylation, and subsequent neuronal death could factors for AD and/or HIV-related impairment. To mimic this clinical condition, we generated mice with AD-like pathology. We first performed short-term Doxycycline (dox) dosing (54, 108, 216 mg/kg/day) study transgenic whose astrocytes express Tat via activation GFAP/dox-inducible promoter. After one week, mouse brains were examined histologically expression Bcl-xL, Bax, phospho-tau was investigated by Western blotting. next cross-bred these PSAPP model AD. simulate chronic secretion over periods longer than used an optimized dose 54 mg/kg/day on biweekly basis three months; based initial ranging mice. This followed antisera detection A-beta, blot phospho-tau, Bax. significantly induced neuron degeneration phosphorylation mice, dox dependently (P<0.001) most robust effects dose. In long term study, similar observed PSAPP/Tat dox. These also showed more (P < 0.05), neurodegeneration, apoptotic signaling, 0.05). conclusion, promotes pathology provide framework which to identify new mechanisms involved infected population, possible treatments. Additional works will needed fully characterize mechanism(s) HIV- amyloid uncover viral promoting general.