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The First Case Of Alzheimer’s Disease: Original Brain Sections Found

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Scientists at the Max Planck Institute of Neurobiology, Martinsried/Germany, and at the University of Munich have rediscovered brain sections of the first case of Alzheimer's disease. A special report is soon to be published in the journal Neurogenetics. Alzheimer's disease is the most common cause of dementia in adult life and affects many million people worldwide. The frequency of the disease is expected to increase rapidly during the next decades due to the growing age of human populations.

Alois Alzheimer first reported on the disease, which was named after him by Emil Kraepelin in 1910, at the 37th Meeting of the Southwest German Psychiatrists in Tübingen on November 3, 1906. Alzheimer described a 51-year-old woman who had come under his care in 1901 while he worked as an attending physician in the Frankfurt Asylum. The original case file of this patient, Auguste D., was discovered recently, and it has been speculated that the patient's dementia was not caused by the typical neurodegeneration of Alzheimer's disease but by arteriosclerosis of the brain. Unfortunately, the brain sections on which Alzheimer's original diagnosis was based remained lost for decades.

A search for the tissue material of this first case of Alzheimer's disease was initiated in Munich because Alzheimer had moved here in 1903 to join the Royal Psychiatric Hospital. In his 1907 publication, Alzheimer acknowledges his former boss, Prof. Sioli in Frankfurt, for "letting him have for examination" the central nervous system of Auguste D. Thus, it seemed likely that Auguste D.'s brain was sent to Alzheimer in Munich after the patient had died in Frankfurt on April 8, 1906. But where to look precisely?

Alois Alzheimer actually published two papers on the disease that now bears his name. Each of these papers contains clinical as well as pathological data on a patient Alzheimer had seen at the hospital. Alzheimer's report on Auguste D. is not a full-size research paper but an abstract summarizing the presentation he gave in Tübingen. In contrast, numerous figures, mainly drawings, which include several examples of the histopathology of his first case were published by Alzheimer in a large article in 1911 together with a second case report. In the latter paper, Alzheimer gives a detailed description of the clinical history and the histopathology of a 56-year-old man, Johann F., who also suffered from presenile dementia.

Led by the biographical data of Johann F. provided in Alzheimer's 1911 paper, an extensive search first turned up histological sections of this second case (Neurogenetics 1997; 1: 73-80). Yet, it is the same collection of material belonging to Alzheimer's laboratory where the histological slides from Auguste D.'s brain have now been found. Examination of these tissue sections showed a large number of neurofibrillary tangles and amyloid plaques in the cerebral cortex of Alzheimer's patient ("neurofibrillary tangles" represent changes in the cytoskeleton of nerve cells which are often associated with cell death, and "amyloid plaques" are extracellular deposits of a probably neurotoxic substance). Thus, taking the clinical picture of Auguste D. into account, Alois Alzheimer's first case represents a typical example of Alzheimer's disease also according to today's standards. Genotyping for the apolipoprotein E epsilon 4 allele revealed absence of this Alzheimer disease "risk factor" but at the same time demonstrated that mutation analysis of the more than 90 year old brain tissue is still feasible.

A comparison of the neuropathology of Auguste D. with that of Alois Alzheimer's second published patient, Johann F., is interesting since it represents an early illustration of the spectrum of Alzheimer's disease as we understand it today. The special importance of the case of Auguste D. lies in the fact that it marks the beginning of Alzheimer disease research and that the neurofibrillary tangles, which now represent an important topic of neuroscience research in their own right, were first described in her brain

Source: Max Planck Institute Press Release: March 23, 1998

Contact: Manuel B. Graeber, M.D., neuropat@neuro.mpg.de, Fax: +49-89-8995-007

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