Amyloid β protein (Aβ) removal by neuroglial cells in culture

The microglial phagocytic role with specific plaque types in the Alzheimer disease brain

“…Furthermore, astrocytic-derived IL-4 inhibited microglial phagocytic activity in vitro [59]. Similarly, cultured astrocytes were incapable of clearing A␤ fibril deposits, and these cells released glycosaminoglycase-sensitive molecules that inhibited the subsequent removal of A␤ by cultured microglia [54]. Inhibition of microglia was also observed in a separate study where nitric oxide (NO)-related oxidative brain damage was promoted by the microglial cytokine TNF-␣ [41], whereas astrocytes exerted, via the release of TGF-␤, a negative feedback that inhibited microglial NO production [55].…”

“…When human-derived dense-core amyloid plaques were injected into the rat brain, astrocytes were activated subsequent to the microglia activation [24]. Interestingly, the local presence of astrocytes inhibited the microglial ability to ingest plaques or A␤ in vitro [19,54]. Without the astrocytes in the cultures, microglia rapidly (within 2 h) phagocytosed, broke apart and cleared the senile plaques.…”

“…In reference to plaque formation, the possibility that microglia could create any plaque type de novo is even more unlikely since they do not express detectable levels of amyloid precursor protein (APP) mRNA, implying that these cells are incapable of synthesizing or producing significant A␤ from endogenous APP [32,54]. Therefore, microglia cells are not necessary for the production of A␤ plaques.…”

Inflammatory mechanisms in Alzheimer disease: the role of beta-amyloid/glial interactions

“…In That microglia can respond to local environmental factors in a neurodestructive manner is well estabcontrast, cultured microglia have been shown to exhibit only limited effectiveness in degrading purified lished, and highlights the recognized role for these amyloid cores in vitro, 48 though being able to rapidly inflammatory drug that inhibits prostaglandin synthesis and can retard leukocyte motility, 56 has been internalize purified A␤. 49 As the phagocytic process can trigger secretion of cytotoxic substances, 37 the shown to significantly lessen the diminution in cognitive performance exhibited by AD patients over a 6-response to deposits of A␤ in vivo may be dependent upon A␤ uptake, degradation and processing by perimonth period, when contrasted with placebo treatment of other AD-afflicted individuals. vascular macrophages, or, alternatively, initiated by 'frustrated phagocytosis' of the aggregated peptide by…”

Congo Red Inhibits Proteoglycan and Serum Amyloid P Binding to Amyloid β Fibrils

“…We (Brunden et al, 1993;Gupta-Bansal et al, 1995) and others (Buee et al, 1993;Snow et al, 1995) have demonstrated that various proteoglycans bind with relatively high affinity to A/I fibrils, and in doing so protect the amyloid peptide from both proteolytic and cellular (Shaffer et al, 1995) degradation. The localization of proteoglycans to senile plaques (Snow et al, 1988(Snow et al, , 1992DeWitt et al, 1993) is consistent with the possibility of their contributing to plaque stability, and Snow et al (1994) demonstrated that heparan sulfate proteoglycan appears to increase A 1@ duration after coinjection into rat brain.…”