Alzheimer's disease: recent advances and future prospects.

will be missed. Each author must do his best, and the editor, advised by his referees, must judge whether that best is good enough. If the editor decides to publish his readers can judge and comment, either privately or in the correspondence column of the journal, if prior claims have been overlooked. They frequently do. Alzheimer's disease: recent advances and future prospects Recent years have seen major advances in our understanding of the neurochemical basis of dementia of the Alzheimer type. Its distinctive neuropathological features include plaques, neurofibrillary tangles, and other changes, but three reports in 1976-81-3 also described appreciable reductions in the activity of the enzyme choline acetyltransferase (which synthesises acetylcholine) in cerebral cortex from patients who had died of dementia of the Alzheimer type. These studies generated considerable interest in the cholinergic system in dementia: the currently influential theory that cholinergic dysfunction underlies the clinical features has recently been well reviewed by Coyle, Prince, and DeLong.4 Reductions in cortical choline acetyltransferase activity in postmortem or biopsy samples of brain occur in specific association with the classical neuropathological changes of Alzheimer's disease: they are not found consistently, for example, in multi-infarct dementia. Furthermore, the severity of the neuropathological changes is associated with the extent of the reductions in choline acetyltransferase and cognitive impairment.5 6 Alzheimer type neuropathological changes are most pronounced in the temporal cortex and hippocampus and so are the reductions in choline acetyltransferase activity; these changes may be responsible for the defects in new learning. Neocortical neuropathological lesions and reductions in choline acetyltransferase are more pronounced in patients with a younger age of onset,7 and these changes might underlie apraxias, aphasias, and agnosias. Neuroanatomical studies suggest that the cortex does not contain intrinsic cholinergic cell bodies, but that it receives an extrinsic innervation of cholinergic nerve terminals originating from subcortical neurones of the substantia innominata, nucleus of the diagonal band of Broca, and septal nuclei.4 These areas are affected by Alzheimer type neuropathological lesions and, in one study, by neuronal fallout and reductions in cholinesterase staining which may indicate loss of cholinergic neurones.4 Rossor et a18 found substantial reductions of choline acetyltransferase activity in postmortem samples of the substantia innominata, whereas most other subcortical samples showed minor changes. If confirmed, these findings suggest that reductions in cortical choline acetyltransferase in Alzheimer's disease result in part from degeneration of cholinergic neurones of the substantia innominata. Probably predegenerative changes …