Figure 4. Proposed mechanisms leading to impaired intra-macrophage Aβ degradation and facilitated extracelluar Aβ fibrillogenesis.

Phagocytosed Aβ fibrils can be retrograde transported into aggresome and then refolding occurs with the help of chaperone molecules such as Hsp70; later they can be degraded by IDE or lysosomal enzymes, or excytosed. Endocytosed Aβ fibrils can also be degraded via endosome-lysosome pathway. HIV might impair Aβ fibrils degradation in macrophage through elevating TNF-α and IFN-γ (inhibitory for Aβ fibrils degradation), decreasing IL-4 and IL-10 (stimulatory for Aβ fibrils degradation), and blocking endosome-lysosomal pathway, raising a possibility that Aβ may be co-leased with virions into extracelluar space where it can serve as a seed for fibrillogenesis.