Evolutionary perspectives on amyloid and inflammatory features of Alzheimer disease

We propose that the amyloid deposits in senile plaques of Alzheimer's Disease (AD) result from ancient mechanisms in wound-healing and inflammatory processes that preceded the evolution of the inducible combinatorial immune responses characteristic of jawed vertebrates. AD plaques are unlike active plaques in MS, because antibodies, T-cells and, B cells are not conspicuous components of senile plaques or other loci of degeneration. However, senile plaques contain amyloids and other inflammatory proteins of ancient origin that appear to be made by local brain cells, including neurons, astrocytes, and microglia. We describe a highly conserved 16-mer found in pentrakins from mammals and from the horseshoe crab. The senile plaque thus provides a novel opportunity to study primitive features of complement-mediated inflammatory responses in the absence of immunoglobulins.