Neurochemical pathology and therapeutic strategies in degenerative dementia

Abstract

The complex pathology of Alzheimer's disease is reviewed in relation to: structural abnormalities such as plaques, tangles and synapse loss; disturbances of the cholinergic, noradrenergic, 5-HT and peptide neurotransmitter systems; the involvement of specific proteins including amyloid precursor protein and microtubule-associated tau; signal transduction systems; and neurotrophic factors. Comparisons are made between classical Alzheimer's disease and Lewy body dementia, which differ in respect to the incidence of psychosis, episodic disturbances of consciousness, the extent of the cholinergic abnormality and the occurrence of both Lewy bodies and tangles—differences which are likely to be of practical importance in relation to the design of rational therapy. Current trends in dementia therapy, assessed on the basis of remits of recent drug trials, generally indicate some benefits with many of the different agents being tested, and emphasize the existence of subgroups of responders. The importance of appreciating the heterogeneity of the pathological process in the future design of dementia therapy is highlighted