Abstract
As we identify the loci involved in late onset neurodegenerative disease, we are finding that the majority of them are involved in damage response processes. In this short review, I propose that it is partly a failure in these damage response processes which underlie late onset disease and that the resultant pathology is a marker of the type of damage response which has failed: microglial clearance of damaged neuronal membranes in Alzheimer's disease (AD), ubiquitin proteasome clearance in the tauopathies, and lysosomal clearance in Parkinson's disease (PD). In this review, I outline this relationship. This article is not intended as a comprehensive review of the cell biology of any of these disorders but rather a summary of the evidence that the genetics and pathology of these disorders appear to point, in each case, to the removal of misfolded proteins as a critical process in disease pathogenesis.