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Alzheimer's disease
  1. J M S PEARCE
  1. 304 Beverly Road, Alunby, Hull HU10 7BG, UK

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    At a psychiatric hospital in Frankfurt, a 51 year old woman (Auguste D), sought help because her family had noticed that she had become uncharacteristically jealous of her husband, and soon became forgetful and tended to get lost. She was fortunate to end up in the hands of Alois Alzheimer, in November 1901.1 When she eventually died in 1906, her brain was sent to Alzheimer, then working in Munich. Alzheimer reported the necropsy of 8 April 1906 to a conference in Tübingen, on 3 and 4 November 1906. An abstract of this report was published in 1907: The Frankfurt archive* has recently been recovered.2

    “A woman, 51 years old, showed jealousy towards her husband as the first noticeable sign of the disease. Soon a rapidly increasing loss of memory could be noticed. She could not find her way around in her own apartment. She carried objects back and forth and hid them. At times she would think that someone wanted to kill her and would begin shrieking loudly. In the institution her behaviour bore the stamp of utter perplexity. . . . Periodically she was totally delirious, dragged her bedding around, called her husband and her daughter, and seemed to have auditory hallucinations.

    . . . “The generalised dementia progressed however. . . . After 4 years of the disease death occurred. At the end, the patient was completely stuporose; she lay in her bed with her legs drawn up under her . . .”

    The necropsy disclosed a generally atrophic brain without macroscopic lesions. The large brain vessels were altered by arteriosclerosis. Alzheimer found

    “ . . .peculiar changes of the neurofibrils...(which) are eventually seen clustering together in thick bundles which emerge at the surface of the cell and miliary foci distinguishable by the deposit in the cerebral cortex of a peculiar substance which can be recognised without stain and is, in fact, very refractory to staining.”3

    Later these changes were called respectively neurofibrillary tangles and amyloid plaques. Alzheimer did not claim that he had found a new disease.4 He was impressed by the histological variation of the neuropathological process, which he did not yet understand. He was keen to show the value of newer histological techniques in psychiatric illnesses that he believed resulted from organic brain diseases.

    A year later, his colleague Francesco Bonfiglio (1883–1966) published a second case, and two years later another Italian, Gaetano Perusini (1879–1915), described four cases: two of them were the cases described by Alzheimer and Bonfiglio. They too believed that they had observed an unusual variant of senile dementia. Emil Kraepelin introduced the term Alzheimer's disease, in the 8th edition of his textbook Compendium der Psychiatrie (1910). Kraepelin knew of Alzheimer's two cases, but also knew of Gaetano Perusini's two new cases. Kraepelin thought that these four patients were significantly different from the usual senile dementias; therefore he categorised them as presenile dementia. Alzheimer did not share this view at this stage. A case he described in 1911 showed no neurofibrillary tangles, and he thought that the plaques were less important. He had found that plaques and tangles were sometimes inconspicuous in patients with severe dementia. Thus began a lasting argument: Was Alzheimer's disease the same as, or was it a variant of senile dementia? Was the disease he had found simply an aging process, or was there some other degenerative factor in operation?5

    Alzheimer's disease now covers a range stretching from the presenile into the senile period. The β-amyloid peptides at the core of senile plaques come from an amyloid precursor protein APP that plays a part in neuronal growth and neurotoxicity.6 Chromosome 21, the site of the trisomy of Down's syndrome, contains the gene for APP. Mutations in presenilin (PS)-1 and -2, located on chromosome 14 and 1 respectively, are the major association with early onset familial Alzheimer's disease (FAD). FAD has also been linked to mutations in the amyloid β precursor protein (β PP). The presence of the apolipoprotein E4 allele on chromosome 19 is a risk factor for late onset AD.7 There is evidence of an AD susceptibility locus on chromosome 128 and possibly on other chromosomes.

    Alzheimer was born at Ochsenfurter Strasse 15 A in Marktbreit-am-Main, the son of a notary. He attended medical schools in Berlin, Wurzburg, and Tubingen, becoming an internist at Frankfurt in 1887–8. He was joined by Nissl, starting a lifetime collaboration. Emil Kraepelin (1856–1926), known as the Linnaeus of Psychiatry, expressed scepticism about pathology to Oskar Vogt: “anatomy can contribute nothing to psychiatry.” Despite this, Kraepelin attracted first Nissl, then young Alzheimer to Heidelberg in 1902. Alzheimer devoted his attention to the histopathology of general paralysis for the insane (GPI), dementia, and cerebral arteriosclerosis.9

    He worked with Wilhelm Erb (1840–1920) and became his close friend. In 1894, Alzheimer received a telegram from Erb, who accompanied Otto Geisenheimer, a banking director, on a scientific expedition in Africa. Geisenheimer suffered a crisis of GPI, in which Alzheimer had become a recognised expert. Alzheimer hurried to Algeria, but his efforts were in vain. However, Geisenheimer's widow, Cecile, weeks after her husband's death, asked Alzheimer to marry her. They had three children but she predeceased him.

    Alzheimer followed Kraepelin to Munich in the Anatomisches Laboratorium. Popular as a teacher, he spent hours poring down the microscope, always a cigar, forgotten and unfinished on the bench. As he moved to the next student another cigar was lit and quickly placed at his side; by the end of the day 20 or more large cigar stumps were strewn around the laboratory.

    He was instrumental in the late conversion of Kraepelin to clinical-anatomical correlation in psychiatry. He moved to the chair of psychiatry in Breslau in 1912, but on arrival was taken to hospital with cardiac symptoms that delayed the start of his work. During the first world war he was without assistants and gradually longstanding rheumatic carditis relapsed; and he died in 1915, aged 52.

    Additional biography:

    Hoff P. Alois Alzheimer 1864–1915. An overview of his life and work on the occasion of his 125th birthday.Nervenarzt1989;60:332–7. Kircher T, Wormstall H. Alois Alzheimer (1864–1915): student days and first scientific activities. J Geriatr Psychiatry Neurol1997;10:127–9

    References

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    Footnotes

    • * In 1992 and 1997, the histological slides of Alzheimer's original cases were rediscovered and re-examined in Munich. This material was found at the Institute of Neuropathology, Munich. Kohshiro Eujisawa of Tokyo had through Henry deE Webster of the NIH in Bethesda, prompted the rediscovery of Alzheimer's cases. Histological and molecular genetic findings obtained on the tissue sections have been reported (Neurogenetics1997;1:73–80; 1998;1:223–28).

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