Alzheimer's Disease and Inflammation
For many years the pharmaceutical industry has invested at least ninety percent of its Alzheimer drug development resources in amyloid-targeting candidates, without any substantial and robust success. It is high time for a change of focus; and an alternate perspective is provided by inflammation.
This is not a new approach; in fact a very large body of research links Alzheimer's disease to inflammation in the brain. It has long been known that the outside of actively growing amyloid plaques is surrounded by inflamed brain tissue which is highly damaging to neurons. However, inflammation markers all but disappear when the plaque stops growing and becomes a comparatively harmless amyloid deposit.
As Dr. Joseph Rogers, one of the pioneers of brain immunology, states in the video produced for the U.S. National Institutes of Aging, inflammation is always going to be a two-edged sword. The immune system attacks biological matter that is foreign, degraded, or (as is the case with beta-amyloid) misprocessed. But once activated it also turns itself on healthy tissue -- the concept being that the body will regenerate this collateral damage later. The brain however cannot easily regenerate.
In October 2013 two scientists from the University of British Columbia stated in a landmark paper:
"We suggest that [Abeta itself or its oligomeric forms], in itself, cannot be the cause of Alzheimer's disease because demonstrating such toxicity requires micromolar concentrations of these Abeta forms, while their levels in brain are a million times lower in the picomolar range. Alzheimer's disease probably results from the inflammatory response induced by extracellular Abeta deposits, which later become enhanced by aggregates of tau. (...) Utilization of antiinflammatory agents early in the disease process remains an overlooked therapeutic opportunity." (Acta Neuropathol. 2013; 126(4):479-497 - see the abstract)
An equally recent paper states, in a journal from the highly reputed Nature Publishing Group:
"Studies in AD brains have shown an upregulation of complement molecules, pro-inflammatory cytokines, acute phase reactants and other inflammatory mediators that could contribute with the neurodegenerative process. Clinical trials and animal models with non-steroidal anti-inflammatory drugs (NSAIDs) indicate that these drugs may decrease the risk of developing AD and apparently reduce Aβ deposition." (Front Integr Neurosci. 2013; 7:59 - see the abstract)