A Tale of Two Scientists

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I haven’t posted here in a while, as I’ve been busy building my new site, designed for the support of caregivers. I invite you to check it out at http://www.exploringdementia.com

In 1907, two very important papers were published. The author of one paper went down in history, as the saying goes, while the other eventually faded into relative obscurity until just recently.

The first of these two men was Dr. Alois Alzheimer, famous for his work in helping to define the disorder that now bears his name. He was born in Bavaria, and earned his medical degree at Wurzberg University in Germany. Soon after graduating, he began work in the Asylum for Lunatics and Epileptics in Frankfurt. In 1901, he observed a patient who exhibited symptoms very similar to those observed in someone with senile dementia. However, Auguste Deter was only 51 years old.

Alzheimer spent a great deal of time in the ensuing years observing Frau Deter and chronicling the development of her disease. Eventually, he moved to Munich, and in 1902 began work at the Royal Psychiatric Clinic there. When Frau Deter died in 1906, he requested that her medical records and her brain be sent to him for further study. Upon autopsy, he discovered the now-characteristic shrinking of the cerebral cortex as well as the presence of neurofibrillary tangles and neuritic plaques.

Going on to publish a paper on the subject, in 1907, Alzheimer described Deter’s case at some length. He was not the one to name this newly-discovered disease after himself, however. That honor fell to Dr. Emil Kraepelin, Director of the clinic where Alzheimer worked at the time of his discovery, when he published his textbook “Psychiatry” in 1910. Kraepelin is a well-respected name in the scientific community, in his own right, for his work in the fledgling field of neuropsychiatry – specifically in the study of schizophrenia and other disorders.

At around the same time period that Alzheimer was doing his research, a scientist named Dr. Oskar Fischer, was working at the German University in Prague. From 1900 to 1909, he worked first in the Department of Pathological Anatomy, and then later moved to the Department of Psychology. He investigated sixteen cases of senile dementia – particularly the cerebral cortexes of these patients – using a number of different staining techniques. He not only described the presence of plaques in 12 of these individuals, but also was the first person to describe what is now known as the neuritic plaque. Plaques were not observed in the brains of 10 control cases, 10 psychotic individuals, and 45 patients with neurosyphilis.
Fischer went on to describe the appearance of these plaques, both as he initially observed them and also as they grew in size. His use of the word “neurofibrils” to describe the appearance of certain components of the plaques has persisted to this day, found in the modern term “neurofibrillary tangles.”

Moving on in his research, Fischer then began to investigate whether the clinical symptoms of these 12 individuals with senile dementia differentiated them from the other test cases. He linked the presence of plaques with a diagnosis of presbyophrenia, a diagnosis commonly used in the early years of the 20th century. This was considered to be a form of dementia, including behaviors such as confabulation, significant memory loss, hyperactivity, disorientation, elevated mood, and a preservation of “social graces.” It was thought to be either a form of Korsakoff’s psychosis or senile dementia. However, the term has vanished from current usage. Those four individuals who did not have plaques were considered to have exhibited senile dementia, thus identifying the two conditions as separate diseases.

In subsequent research, Fischer went on to describe eight stages of plaque development. He likened plaque formation to the inflammatory process, especially interesting now in view of the current research in that vein. (It was only when the state of immunohistochemistry had evolved sufficiently that Fisher’s theories were able to be validated.)

The work of Alzheimer and that of Fischer are considered to complement each other, with their use of staining techniques to identify the neuritic plaques and neurofibrillary tangles being the major point that made their work stand out over that of others. Interestingly, Alzheimer also discovered what later became known as “Pick’s bodies” in what later became known as Pick’s disease or frontotemporal dementia. (The director of the clinic where Fischer did the bulk of his work was Dr. Arnold Pick, now famous for his work in the definition of FTD.)

The two scientists disagreed on a number of matters. For instance, Alzheimer took issue with Fischer’s theory that the plaques had a link with presbyophrenic dementia. While he agreed that plaques were a distinctive feature of senile dementia, he did not think that they actually caused the disease, as Fischer did. Alzheimer did actually give Fischer credit for helping to draw attention to plaques in the diagnosis of senile dementia. He considered that the cases of presenile dementia that he and Fischer had both described to be a sub-type of senile dementia, rather than an entirely new disease. Fischer also disagreed that a new disease was being reported. The two men differed in their opinion on the formation and the significance of the tangles.

So, why do we speak of Alzheimer’s disease, and not Fisher’s disease? In the years immediately following the work of both men, we do find references in the literature to “Fischer’s plaques.” Alzheimer himself actually used the term in a paper he wrote in 1911. The terms presbyophrenic dementia and Alzheimer’s disease were both in usage as late as 1949. However, by 1955, textbooks that had previously used Fischer’s name to denote the disease had been changed to use the term Alzheimer’s disease exclusively. Fisher’s work was reported as being obsolete.

Some credit other factors as playing a part in Fischer’s legacy. Despite teaching there for 17 years, Fischer was never awarded tenure at the German University, and in fact his appointment was revoked in 1939 as the university began to quietly remove all Jewish faculty in anticipation of the Nazi take-over. Fischer attempted to continue a private practice until 1941, when he was arrested by the Gestapo. This eventually led to his imprisonment and death in a Nazi concentration camp in 1942. The German University, where he had done so much work, was likewise closed down in 1945. Fischer did not have any students who continued his work, as Alzheimer did.

By contrast, Alzheimer worked under Dr. Kraepelin, who not only named the disease after him, but was also one of the most influential psychiatrists of his time. The Munich institute continued for many years, and when Alzheimer ceased his work there in 1912, he was succeeded by Spielmeyer, one of the most respected histopathologists of his time. It has also been speculated that, because the schools where the two men worked were rivals, Kraepelin was quick to gain recognition for his school as well as for Alzheimer. However, even though Kraepelin coined the term Alzheimer’s disease in 1910, it was not until the 1970s that the term became widely used to describe patients with senile dementia.

http://www.ncbi.nlm.nih.gov “Presbyophrenia: the rise and fall of a concept”
“Oskar Fischer and the study of dementia,” by Michel Goedert, in Brain, 2009, 132.
“Oskar Fischer,” Wikipedia
“Prague: What Say You, Alois – Should it be ‘Alzheimer-Fischer’ Disease?” Gabrielle Strobel, http://www.alzforum.org

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