The molecular and cellular pathogenesis of dementia of the Alzheimer's type an overview

The pathogenesis of dementia of the Alzheimer's type (DAT) remains elusive. The neurodegeneration occurring in this disease has been traditionally believed to be the result of toxicity caused by the accumulation of insoluble amyloid-beta 42 (AB) aggregates, however recent research questions this thesis and has suggested other more convincing cellular and molecular mechanisms. Dysfunction of amyloid precursor protein metabolism, AB generation/aggregation and/or degredation/clearance, tau metabolism, protein trafficking, signal transduction, heavy metal homeostasis, acetylcholine and cholesterol metabolism, have all been implicated etiologically especially as to production of neurotoxic by-products occurring as a result of a specific process derangement. In this paper, these and other research directions are discussed as well as their implications for future therapies. The relationship of the proposed abnormal molecular and cellular processes to underlying genetic mutations is also scrutinized, all in an attempt to stimulate further insight into the pathogenesis of, and thus therapeutics for this increasingly prevalent disease.