100 years of Alzheimer’s Disease

alz-figs-fig1.jpgOn November 4th, 1906, during a lecture at the 37th Conference of South-West German Psychiatrists in Tübingen, the German neuropathologist and psychiatrist Alois Alzheimer (1864-1915, left) described “eine eigenartige Erkrankung der Hirnrinde” (a peculiar disease of the cerebral cortex). In the lecture, he dicussed “the case of a patient who was kept under close observation during institutionalisation at the Frankfurt Hospital and whose central nervous system had been given to me by director Sioli for further examination”. This was the first documented case of the form of dementia that would subsequently bear Alzheimer’s name.

Alzheimer was born on June 14th, 1864, in the small Bavarian town of Marktbreit. He attended Aschaffenburg, Tübingen and Berlin universities before obtaining his medical degree from Würzburg University in 1887. In the same year, he completed his Ph.D. thesis on the wax-producing glands of the ear, based on experiments he had carried out in the laboratory of Rudolf Albert von Kölliker, the Swiss physiologist who made valuable contributions to our undertanding of the organization of the nervous system.

Within months of obtaining his medical degree, Alzheimer began working at the Städtische Heilanstalt für Irre und Epileptische (Hospital for the Mentally Ill and Epileptics) in Frankfurt. There, Alzheimer studied psychiatry and, with Franz Nissl, who had developed a method for staining nervous tissue, undertook a comprehensive investigation of the pathology of the nervous system.

On November 25th, 1901, a 51-year-old woman named Auguste Deter (below right) was admitted to the hospital, and was examined by Alzheimer. Deter at first presented with impaired memory, aphasia, disorientation and psychosocial incompetence (which was, at that time, the legal definition of ‘dementia’); her condition gradually worsened, and she started losing other cognitive functions and experiencing hallucinations. Because of her age, Deter was diagnosed with presenile dementia; today, the diagnosis would be early-onset Alzheimer’s Disease, which is defined as development of the condition before the age of 65.

augusted.jpgDeter died in April 1906, aged 55. By that time, Alzheimer had left Frankfurt, and was working under Emil Kraepelin at the Royal Psychiatric Clinic in Munich. Hearing of Deter’s death, he requested from Sioli, the director of the Frankfurt institution where Deter had been, that her medical records be sent to him.

Psychiatrists rediscovered Deter’s medical records in 1995, in the archives at the University of Frankfurt. The 32-page file contained Deter’s admission report, and three different case histories, including notes written by Alzheimer himself. Most of the file is written in an outdated German script called Sütterlinschrift. The file also contains a small sheet of paper on which there are samples of Deter’s handwriting (below left), demonstrating what Alzheimer named ‘amnestic writing disorder’.

An extract from the file, written by Alzheimer and dated November 26th, 1901 (below right) reads:

She sits on the bed with a helpless expression. What is your name? Auguste. What is your husband’s name? Auguste. Your husband? Ah, my husband. She looks as if she didn’t understand the question. Are you married? To Auguste. Mrs D? Yes, yes, Auguste D. How long have you been here? She seems to be trying to remember. Three weeks. What is this? I show her a pencil. A pen. A purse, key, diary and cigar are identified correctly. At lunch she eats cauliflower and pork. Asked what she is eating she answers spinach. When she was chewing meat and asked what she was doing, she answered potatoes and horseradish. When objects are shown to her, she does not remember after a short time which objects have been shown. in between she always speaks about twins. When she is asked to write, she holds the book in such a way that one has the impression that she has a loss in the right visual field. Asked to write Auguste D., she tries to write Mrs and forgets the rest. It is necessary to repeat every word. Amnestic writing disorder. In the evening her spontaneous speech is full of paraphrasic derailments and perseverations.

                                       file1.jpg notes.jpg

Ironically, it appears that Deter’s death was caused not by the pathologies now associated with Alzheimer’s Disease but rather by arteriosclerosis (hardening of the arteries) in the brain. When she died, she was examined by two of Alzheimer’s colleagues, who recorded the death in her medical file as follows:

During the morning exitus letalis; cause of death: septicaemia due to decubitus; anatomical diagnosis: moderate hydrocephalus (external internal); cerebral atrophy; arteriosclerosis of the small cerebral blood vessels; ? ; pneumonia of both inferior lobes; nephritis.

The year after Deter’s death, Alzheimer described her histopathology to psychiatrists at the conference in Tübingen:

In the centre of an otherwise almost normal cell there stands out one or several fibrils due to their characteristic thickness and peculiar impregnability. Numerous small miliary foci [amyloid plaques] are found in the superior layers. They are determined by the storage of a peculiar material in the cortex. All in all we have to face a peculiar disease process [which has] been verified recently in large numbers.


L to R: A Nissl-stained tissue section from Auguste D.’s brain, a Bielschowsky-stained section from the same patient, showing neurofibrillary tangles, and a diagram of the tangles from a 1911 research paper by Alois Alzheimer.

Another irony is that it may have been someone other than Alzheimer who ‘discovered’ Alzheimer’s Disease. The condition described by Alzheimer at the psychiatry conference in 1906 had already been described by Oskar Fischer, Francesco Bonfiglio and Graetano Perusini. It was largely due to Emil Kraepelin, Alzheimer’s boss at the clinic in Munich, that the condition is now known as Alzheimer’s Disease. Kraepelin, who first classified schizophrenia, included Alzheimer’s description of Auguste Deter’s symptoms and pathology in the eighth edition of his book Psychiatrie, which was published in 1910. In that book, Kraepelin calls the condition ‘Alzheimer’s Disease’ for the first time:

…the autopsy reveals, according to Alzheimer’s description, changes that represent the most serious form of senile dementia… the Drusen [amyloid plaques?] were numerous and almost one-third of the cortical cells had died off. In their place instead we found peculiar deeply stained fibrillary bundles that were closely packed to one another, and seemed to be remnants of degenerated cell bodies… The clinical interpretation of this Alzheimer’s disease is still confused. While the anatomical findings suggest that we are dealing with a particularly serious form of senile dementia, the fact that this disease sometimes starts already around the age of 40 does not allow this supposition [i.e. it should be considered as a new disease]. In such cases we should at least assume a ‘senium praecox’ if not perhaps a more or less age-independent unique disease process.

Alzheimer had described Auguste Deter as an example of dementia in a relatively young person, and did not claim to have discovered the disease. He, and others, were surprised that Kraepelin had named the condition ‘Alzheimer’s disease’, but, nevertheless, the name stuck. Kraepelin had probably named the disease after Alzheimer and exaggerated the novelty of the findings to give his institution more prestige, and to ensure the continuation of research grants. 5 years after the publication of Kraepelin’s book, Alzheimer died of tonsilitis-induced nephritis, aged 51.


  • Graeber, M. B. et al (1997). Rediscovery of the case described by Alois Alzheimer in 1911: historical, histological and molecular genetic analysis. Neurogenetics 1: 73- 80. [Full text]
  • Graeber, et al (1998). Histopathology and APOE genotype of of the first Alzheimer disease patient, Auguste D. Neurogenetics 1: 223- 228. [Full text]
  • Graeber, M. B. & Mehraein, P. (1999). Reanalysis of the first case of Alzheimer’s disease. Eur. Arch. Clin. Neurosci. 249: Suppl. 3 III/10- III-13. [Full text]
  • Maurer, K. et al (1997). Auguste D. and Alzheimer’s disease. Lancet 349: 1546- 49. [Full text]

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9 thoughts on “100 years of Alzheimer’s Disease

  1. Thank you for a great post. I appreciate the addition of the historical perspective and the overall quality of your writing and perceptions. I will be linking to your blog and hope that others will also find and enjoy your writing, as I have.

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