Alzheimer's disease—new approaches to old problems

Summary

The definite diagnosis of Alzheimer's disease (AD) is based upon quantitative estimates of two main neuropathological features: tangles and plaques. The characterization of the principal components of neurofibrillary tangles and plaques identified altered metabolism of tau protein and amyloid protein precursor (APP) to underlie the development of these changes. Here we review research conducted during the last decade aiming to elucidate the pathophysiological mechanisms that lead to the formation of both neurofibrillary changes and extracellular deposits of amyloid. We have specifically focused on three major topics that dominate comtemporary AD research: (i) altered metabolism of APP as a result of mutations of the APP gene; (ii) altered tau metabolism in aging and Alzheimer's-type dementia; and (hi) the role of apolipoprotein s4 allele in the genesis of tau and amyloid pathology.