AMINF: Inflammation and Amyloid from Atoms to Tissue

by J. Berryman and M. Heneka

Amyloid diseases in general have complex and often unknown etiologies, however inflammatory processes are a common feature of the large-scale killers, Alzheimer’s disease and Parkinson’s.

Inflammation is well-characterised as the typical direct cause of AA amyloidosis, and is likely to be a mediating process in the destructive interaction of SARS-CoV2 and amyloid disease. During inflammatory response, reactive oxygen and nitrogen species are produced which interact promiscuously with endogenous molecules, including aggregation-prone peptides. It is already known that inflammatory damage can strongly enhance aggregation and neurotoxicity of Amyloid Beta peptides (Aβ), however, typically for amyloid disease, the picture remains murky as the biochemistry of inflammation is complex, and protective effects have also been reported for similar oxidative inflammatory effects under different experimental conditions. The purpose of this project is to examine the precise molecular and supramolecular changes driven by reactive species released during inflammation and quantitatively discriminate between harmful and beneficial inflammation-driven processes, tracing the thread all the way from atomistic inflammation-driven free radical chemistry up to amyloid disease in three-dimensional human tissue cultures and in mice. Interdisciplinary collaboration, such as the Institute for Advances Studies is designed to foster, is necessary to address this lengthscale-crossing feedback between biological processes at the atomic, molecular, supramolecular, cellular, and tissue levels which are typically studied piecemeal by very different communities with very different tools, leading to a lack of any complete and satisfying understanding. A quantitative multiscale description of these interactions will shed much-needed light on the etiology of neurodegenerative disease, and on its links to inflammatory conditions such as obesity and infection, which today are known of but very little understood. This project proposes to trace a complete and quantitative etiology leading from specific inflammatory stimulus to Alzheimer’s disease, which should provide valuable insight leading ultimately to new therapeutic approaches.


Prof. Michael HENEKA