Activated microglia secreted elevated levels of proinflammatory cytokines (IL1-β, TNF-α, IFN-γ) that can up-regulate BACE1 and APP expression in neurons, resulting in increased Aβ generation. HIV viral protein Tat can be up-taken via LRP into neurons where it can inhibit Neprilysin activity, blocking Aβ degradation. The reduced secretion of anti-inflammatory cytokines (IL-4 and IL-10) also contributes to impaired Aβ degradation. Accelerated perivascular Aβ deposition is a consequence of impaired efflux of Aβ into plasma, and/or inhibition of perivascular Aβ degrading enzymes by viral proteins.