Molecular mechanisms of late life dementias

A brief overview of the molecular pathology of dementia of the Alzheimer ty pe (DAT), frontotemporal dementias (FTD), and Lewy body dementias (LBD) is preceded by a discussion of the evolutionary biological basis for the types of gene action responsible for the emergence of late life dementias. The b eta amyloid cascade theory of the pathogenesis of DAT still predominates, b ut possible upstream events are being explored. Some familial forms of FTD have been shown to result from dominant mutations in the microtubular assoc iated protein tau. A key element in pathogenesis is a shift in the ratios o f various isoforms. Rare forms of Parkinson disease have been associated wi th dominant mutations in alpha synuclein, a protein of probable importance for synaptic plasticity. Aberrations in the metabolism of this protein (whi ch is found in Lewy body fibrillar material) may therefore be of importance to the genesis of some LED cases. (C) 2000 Elsevier Science Inc. Pill righ ts reserved.