Sir

Peter St George-Hyslop and David Westaway discuss the possibility of using Aβ immunization to treat Alzheimer's disease1. They mention the continuing controversy2,3 surrounding the role of extracellular Aβ accumulation and amyloid plaques in the causation of the dementia associated with the disease, referring to this as “an old debate”. What is not widely recognized is how old the question at the centre of this debate actually is.

Alois Alzheimer and his contemporaries4 considered this very question. In a 1911 paper entitled “On certain peculiar diseases of old age”5, Alzheimer writes: “There are cases of indubitable Dementia senilis, in which the plaques are not very numerous. Moreover, as Fischer stresses, they dislocate the nervous structures more than they destroy them. So the loss of cortical tissue due to the plaques cannot be very considerable. Furthermore, in places where plaques are not found in the cerebral cortex, we see the well-known widespread senile sclerotic changes, the lipid-pigmented and granular degenerations of ganglion cells with alterations of their fibrils which Brodmann and Bielschowsky have described in detail, the fibre-formation of the glia, pigment-accumulation in the glia and the degenerative phenomena in the vessel-walls which it is impossible to believe were caused by plaques.

“These changes are found in the basal ganglia, the medulla, the cerebellum and the spinal cord, although there are no plaques at all in those sites or only isolated ones. So we have to conclude that the plaques are not the cause of senile dementia but only an accompanying feature of senile involution of the central nervous system.”

The italics are Alzheimer's and the translation is by Hans Förstl and Raymond Levy6. The paper was written by Alzheimer after his examination of only three patients with the disease. It is a remarkable testament to his meticulous work and originality of thought that 88 years ago he put forward an analysis that is not out of place in the context of the current debate.