• DOI:10.1177/153331750001500404
• Corpus ID: 144484516

The legacy of Alois Alzheimer: An historical perspective

@article{Lefroy2000TheLO,
  title={The legacy of Alois Alzheimer: An historical perspective},
  author={Richard B. Lefroy},
  journal={American Journal of Alzheimer's Disease and Other Dementias},
  year={2000},
  volume={15},
  pages={252 - 255}
}

• R. Lefroy
• Published 1 July 2000
• Biology
• American Journal of Alzheimer's Disease and Other Dementias

for celebration when they came across a parcel containing tissues of a brain autopsy that had been missing for 90-years. Using a new technique, Alois Alzheimer had demonstrated peculiar changes in neurofibrils of the brain cells as well as numerous small miliary foci (later known as plaques). Having been the attendant physician to Auguste D (in keeping with the characteristically modern custom, we know her only by her first name) during her long stay in the Frankfurt Asylum, he was duly impressed by the association between the bizarre behavior he had observed during life and his discovery at autopsy.1 Professor Kraepelin named the disorder ‘Alzheimer’s Disease’ in his Textbook of Psychiatry in 1910—and the activity that it generated has proven to be of major importance since the steep rise in prevalence of the condition during the latter part of the century. The title of his original case report in 1906 was, ‘A new disease of the cerebral cortex,’2 although dementia was not a new phenomenon. Pythagoras in the seventh century BC was one of the many ancient writers who recorded instances of regression in mental capacity.3 What was new, however, was the thesis that the devastating changes in behavior observed during the life of this 51-year old woman were associated with the structural changes in the brain—the plaques and tangles—seen by Alzheimer at autopsy. ‘The change’ he wrote, ‘is concomitant with infiltration by an undetermined metabolic product.’ Although the tissues were missing and have only recently become available for reexamination, Alzheimer’s description and drawings were sufficient to inveigle scientists all over the world into a search for the cause—a search which is still in progress. It is a story worthy of consideration by those who have doubt about the value of organ donation for the purpose of research. What was this ‘undetermined metabolic product’? After years of work in the laboratory the mysterious product was given the name of beta amyloid on account of its similarity to the naturally occurring substance, amyloid.4 The next question was—what was responsible for the presence of this product? Another decade was to pass before further light was cast on the problem. Reference is now made to the post-genome era, but although a hereditary component to dementia had been suspected, the word ‘gene’ had not appeared before Alzheimer made his report; and the precise role of the gene—namely, the determination of the structure of protein in its initial stages—was not apparent until the 1940s.5 Genes have a habit of changing their structure through mutation; could such an event be responsible for determining the formation of the substance that was destroying the brain cells? The hunt was by then being pursued in many laboratories throughout the world, intent on discovering how the gene might be implicated in the formation of the plaques and tangles that Alzheimer had described. Excitement was intense in the late1980s when the gene on a certain chromosome was found to be associated with Alzheimer’s disease (AD). It was then discovered that the association only occurred in a small proportion of individuals with this disease. These were the people affected comparatively early in life (Early Onset Alzheimer’s Disease). Nevertheless, geneticists persisted in their search, particularly since it was discovered that rarely is a