Publications

Abstract

This review concerns how the primary inflammation preceding the generation of certain key damage-associated molecular patterns (DAMPs) arises in Alzheimer's disease (AD). In doing so, it places soluble amyloid beta (Abeta), a protein hitherto considered as a primary initiator of AD, in a novel perspective. We note here that increased soluble Abeta is one of the proinflammatory cytokine-induced DAMPs recognized by at least one of the toll-like receptors on and in various cell types. Moreover, Abeta is best regarded as belonging to a class of DAMPs, as do the S100 proteins and HMBG1, that further exacerbate production of these same proinflammatory cytokines, which are already enhanced, and induces them further. Moreover, variation in levels of other DAMPs of this same class in AD may explain why normal elderly patients can exhibit high Abeta plaque levels, and why removing Abeta or its plaque does not retard disease progression. It may also explain why mouse transgenic models, having been designed to generate high Abeta, can be treated successfully by this approach.