One of the delights of old age psychiatry as a discipline is the scope to work in both biological and social research and to use both medical and psychosocial understanding in working with patients. This rich combination of interests is found in a single individual in Professor Raymond Levy. Few professors are as likely to be found, feet on desk, cigar discretely under desk, perusing Nature as if reading the latest novel. Perhaps this should not be surprising. Scientific journals contain excellent stories and few are more exciting than that of recent work on the molecular neurobiology of Alzheimer's disease (AD). This article reviews one strand of this story-that of tau and its phosphorylation.
Alzheimer described two central and essential lesions in the brain of his eponymous degeneration-plaques and tangles. Plaques have a central core of beta amyloid protein or PAP and much of recent molecular neurobiology concentrates upon the metabolism of the parent compound amyloid precursor protein, APP (McLoughlin and Lovestone, 1995). The discovery that mutations in APP, on chromosome 21, lead to an extremely rare variant of early onset autosomal dominant familial AD suggested to many that amyloid deposition was a central feature of all Alzheimer diseases. A transgenic mouse overexpressing mutated APP forms plaques (Games et al., 1995) and this was taken as further evidence by some that all other pathologies in AD are epiphemonema (Duff and Hardy, 1995). Those interested in PAP, the BAPtists, are often evangelical in promoting their view of the Alzheimer world. The other pathological lesion recognized by Alois Alzheimer is the neurofibrillary tangle which has been shown to be formed from tau protein. Researchers in this area, the TAUists, because of the fundamental importance of tau protein to normal neuronal structure and function, have an inclination towards a larger, more inclusive, but, some might add, more