Alois Alzheimer

He never forgot his cigar!

Alois Alzheimer was born in the small Bavarian town of Marktbreit, where his father was notary public. He attended the universities of Aschaffenburg, Tübingen, Berlin, and Würzburg, where he was granted a medical degree in 1887. That same year he defended his doctoral thesis, on the wax-producing glands of the ear. It was based on experimental research performed in the laboratory of the noted Swiss physiologist and histologist Rudolf Albert von Kölliker (1817-1905).

The years with the lunatics of Frankfurt am Main
The following year, 1888, Alzheimer spent 5 months accompanying a mentally ill women on a journey, before he joined the staff of the city mental asylum in Frankfurt am Main - the Städtische Irrenanstalt – headed by Emil Sioli (1852-1922). Here he commenced his education in psychiatry, and devoted himself to his great interest, neuropathology. Already the year after the distinguished neurologist Franz Nissl (1860-1919) came to work in the same asylum.

Nissl and Alzheimer
Nissl and Alzheimer embarked on an extensive investigation of the pathology of the nervous system, studying in particular the normal and pathological anatomy of the cerebral cortex. This work resulted in the major 6 volume work Histologische und histopatologische Arbeiten über die Grosshirnrinde (Histologic and Histopathologic Studies of the Cerebral Cortex), published between 1906 and 1918.

Alzheimer concentrated his efforts on the patient material, while Nissl above all seems to have done experimental studies of the reaction of the nerve cell and tigroid substance after sectioning their axon. Nissl was probably the more innovative of the two, his energetic and imaginative enthusiasm being complemented and shaped by Alzheimer's powers of deduction as well as his advanced technique in experimental histology. Alzheimer was the careful and dedicated laboratory worker who proved the observations histologically, and was known for his wonderful gift of description of his microscopical findings.

A close friendship arose between the two doctors, working with the patients during daytime, spending evenings and nights at the microscope. In 1895 Nissl moved to the leading German psychiatrist of the time, Emil Kraepelin, in Heidelberg, and later succeeded him as head of the clinic there. Alzheimer was appointed director of the Irrenanstalt in 1895, continuing his research on a wide range of subjects, including clinical studies of manic depression and schizophrenia.

In 1902 Kraepelin, the ”Linnaeus of psychiatry”, invited Alzheimer to work with him in the university psychiatric clinic in Heidelberg, and thus he once more worked with Nissl. In 1903 Alzheimer accompanied Kraepelin to the university psychiatric clinic in Munich, where he was habilitated with a work on differential diagnostics in progressive paralysis. In 1908, he joined the staff of the Psychiatric Institute as ausserordentlicher (associate) professor and succeeded Robert Gaupp (1870-) as director of the clinic's anatomical laboratory. This soon gained international reputation and became a meeting place for several important researcher, among them Ugo Cerletti (1877-1963), Hans Gerhardt Creutzfeldt (1885-1964), Alfons Maria Jakob (1884-1931), Fritz H. Lewy (1885-1950), F. Lotmar, and Gaetano Perusini (1879-1915).

Fruitful years
During the years in Munich Alzheimer described the disease that was to bear his name, but at this time also did microscopical investigations of other nervous diseases. He described, among other things, brain changes in arteriosclerosis and loss of nerve cells in dancing mania – Huntington's chorea – that Alzheimer found to most pronounced in the inner part of the cerebrum, in the corpus striatum. Alzheimer also studied brain changes in epilepsy; among other things he described a comprehensive loss of nerve cells in the hippocampus in a large part of epileptic patients, so-called ammon sclerosis. As early as in 1907, in a lecture, he suggested that the loss of nerve cells at first should not make up a part of the disease, which called the attacks, but instead might be caused by the attack itself. This has been corroborated by later investigations.

Do you remember Alzheimer?
At a meeting of the South-West German Society of Alienists in November 1906 Alzheimer described "eine eigenartige Erkrankung der Hirnrinde" (a peculiar disease of the cerebral cortex) – the clinical and neuropathological features of a Auguste Deter.

Alzheimer had met Auguste Deter in 1901 at the Städtische Heilanstalt für Irre und Epileptische in Frankfurt. She had been admitted on November 25, aged only 51. When she died in 1906 he was working in Munich. Alzheimer met as he was working in Frankfurt. As she died in 1906, aged 55, Alzheimer was working in Munich. When he received the message of her death, he asked his previous chef Sioli to get access to both records and the brain of Augste D.

The woman had become successively unable to care for herself at home and rejected all attempts to help her. Upon hospitalisation her symptoms were disorientation, impaired memory, as well as troubles in reading and writing. The symptoms increased gradually, to hallucinations and a gradual loss of higher mental functions.

The pathological-anatomical investigation of the brain showed the cerebral cortex to be thinner than normal. Alzheimer noted two further abnormalities in the brain. The one being senile plaque, a structure previously described in the brain of elderly people. The other abnormality was neurofibrillar tangles in histological material from her cerebral cortex, a fibre structure of the nerve cells presenting with the use of Bodian’s silver stain. The nerve tangling had not been previously described, and it was mainly this abnormality that defined a new disease.

Due to the low age of Alzheimer’s patient, the disease was long considered a form of presenile dementia. It is now recognized that the same pathological atrophy of the brain is found in many patients of advanced age, and most authorities no longer delimit the term Alzheimer’s disease to presenile cases.

Alzheimer made a preliminary report of his findings in 1906 and provided further details in the following year. In 1910 Perusini published four more cases and emphasized the difference between the condition and senility. Kraepelin agreed with the concept of syndromic identity and proposed that Alzheimer’s name should be attached to the condition. Italian writers favoured the term Alzheimer-Perusini disease but the single eponym is now in general use.

Alzheimer’s second case was a demented 56-year-old man, Johann F. who was admitted to the university psychiatric clinic in Munich on September 12, 1907, and died there on October 3, 1910. This patient had brain changes similar to those of his first patient. Alzheimer and collaborators described this patient the following year. In his work on this case from 1911 Alzheimer therefore interpreted his first patient as an atypical case of senile dementia. At a cellular level he reported the degeneration of the smaller cerebral blood vessels, a process now referred to as Alzheimer's sclerosis.

At this time Alzheimer commenced the study of brain changes in different stages of syphilis, in an attempt to correlate symptoms and pathology. At that time paralysie générale was the most obvious example of an organically conditioned psychosis. Syphilis patients also occupied a large part of the beds in the clinic. The etiological agent had not yet been found and there was no existing laboratory diagnosis. The work resulted in a treatise in 1904 which explained exactly all brain changes in the disease known today. It was based on 170 pathological-anatomically investigated cases over a period of seven years chosen among a total of 320 autopsied patients.

The man with the cigar
His more than ten years in Munich as head of the anatomical laboratory at Kraepelin’s clinic were Alzheimer's best. Students from various countries constantly occupied the twenty seats in the laboratory. Alzheimer alternated between the microscope workstations, spending ample time with each one explaining things as they shared a microscope. Those who attended have described it as an almost unforgettable sight when Alzheimer with his large head bowed over the microscope with the pince nez dangling in a string around his neck, always with a cigar, which would be put down as he commenced his explanations. It is said that at the end of the day there would always be a cigar stump at every student's bench by the microscope, marking his tour in the laboratory.

During the later years of his career Alzheimer concentrated his efforts on the study of changes in glia cells in diseases of the brain. His best-known works from this period were on Westphal-Strümpell pseudosclerosis of the brain, now assumed to be the same as (Kinnier) Wilson’s disease. In this work he distinguished between two forms of changes of the glia cells, termed Alzheimer's type II, and I respectively, based on morphological changes in the nucleus of the glia cells.

The banker's widow
Alzheimer was a close friend of Wilhelm Heinirich Erb, a noted expert on syphilis. It is said that a banker who had contracted the disease had consulted Erb. After the treatment had been completed the banker wanted to show his gratitude and offered to finance a scientific expedition to Africa, on the proviso that he and his wife would accompany the team. Erb saw no objections and the team embarked. The party had just arrived in Algeria when Erb received a telegram reporting that the banker had suffered another nervous breakdown. Erb contacted Alzheimer, who came to Algeria to bring the banker and his wife back to Germany,

When the banker died Alzheimer married his widow and this made him financially independent so that he was able to supplement all the texts he wrote with numerous illustrations.

His wife, Cäcilia Geisenheimer died after only seven years of marriage. One of Alzheimer’s daughters, Gertrude, later married the Breslau physician Georg Stertz, who assumed the chair of psychiatrics at Munich in 1946.

Last years
On July 16, 1912, King Wilhelm II of Prussia signed his certificate of appointment as full professor of psychiatry at the University of Breslau (now Wroclaw, Poland). Alzheimer accepted the invitation and left Munich, but already on the train he felt ill and had to be hospitalised immediately upon arrival. Though troubled by rapidly deteriorating health, he devoted the last three years of his life to research and clinical work, but never was able to commence his university duties in Breslau as intended. His death at the age of 51 was the result of cardiac failure following endocarditis.

Diagnostics of Alzheimer’s disease today is still generally based on the same investigative methods used in 1906. This is remarkable compared with the development of investigative methods for other diseases, and it says a lot about the quality of Alzheimer’s discovery.

Alzheimer never wrote a book of his own, but worked on a large manuscript, Die Anatomie der Geisteskrankheiten (The Anatomy of Mental Diseases) for a textbook on psychiatry, but the paper was never completed.

With Max Lewandowsky (1876-1918) Alzhimer was co-founder and co-publisher of the journal Zeitschrift für die gesamte Neurologie und Psychiatrie.

«Nicht übermässige Bedenken und Lähmende Verzagtheit helfen den Wisenschaften vorwärts und haben ihnen vorwärts geholfen, sondern ein gesunder Optimismus, der in froher Zuversicht nach neuen Wegen der Erkenntnis sucht, da er überzeugt ist, das sie zu finden sein werde.»

• Ueber einen Fall von spinaler progressiver Muskelatrophie mit hinzutretender Erkrankung bulbärer Kerne in der Rinde.
  Sonder-Abdruck aus dem Archiv für Psychiatrie. Bd. XXIII. Heft 2. 1882.
• Über die Ohrenschmaldrüsen.
  Inaugural-Dissertation verfasst und der hohen medicinischen Facultät der Königl. Julius-Maximilians-Universität Würzburg zur Erlangung der Doctorwürde in der Medicin, Chirurgie und Geburtshilfe vorgelegt von Alois Alzheimer. Cand. Med.
  In short: Doctoral dissertation.
  Würzburg, Druck und Verlag der Stahel'schen Univer.-Buch- & Kunsthandlung, 1888.
• Histologische Studien zur Differentialdiagnose der progressiven Paralyse.
  Habilitationsschrift zur Erlangung der Venia legendi in der Psychiatrie vorgelegt der hohen medicinischen Facultät der Ludwigs-Maximilians-Universität zu München von Dr. med. Alois Alzheimer. Appr. Arzt.
  His habilitation thesis. Jena, 1904.
• Über einen eigenartigen schweren Krankheitsprozess der Hirnrinde.
  Zentralblatt für Nervenkrankheiten, 1906, 25: 1134.
  Zentralblatt für Nervenkrankheiten, 1907, 30: 177-178.
• Ueber eine eigenartige Erkrankung der Hirnrinde.
  Allgemeine Zeitschrift für Psychiatrie und psychisch-gerichtliche Medizin, Berlin, 1907, 64:146-148.
• 25 Jahre Psychiatrie. Ein Rückblick anlässlich des 25-jährigen Jubiläums von Professor Dr. Emil Sioli als Direktor der Frankfurter Irrenanstalt.
  Archiv für Psychiatrie und Nervenkrankheiten, Berlin, 1913, 52: 854-866.
• Histologie und Histopathologie. Written with Franz Nissl.
  Posthumous, in: Arbeiten über die Grosshirnrinde mit besonderer Berücksichtigung der pathologischen Anatomie der geisteskrankheiten. Jena, 1921.
• Monographien aus dem Gesamgebiete der neurologie und Psychiatrie. With Felix Lewandowsky. On Alzheimer and "his" disease
• Anonymous:
  Alois Alzheimer (1864-1915). Neuropathologist.
  Journal of the American Medical Association, May 12, 1969, 208 (6): 1017-1018.
• T.G. Beach:
  History of Alzheimer's disease: three debates.
  Journal of the History of Medicine and Allied Sciences, 1987, 42 (3): 327-349.
• G.E. Berrios:
  Alzheimer's disease: a conceptual history.
  International Journal of Geriatric Psychiatry, November/December 1990, 5 (6): 355-365.
• P.J. Fox:
  Alzheimer's disease: an historical overview.
  American Journal of Alzheimer's Disease and Related Disorders, fall 1986, 1 (4): 18-24.
• K. Bick, L. Amaducci & G. Pepeu, editors:
  The early story of Alzheimer's disease
  Translation of the historical papers by Alois Alzheimer, Oskar Fischer, Francesco Bonfiglio, Emil Krapelin, and Gaetano Perusini.
  Padova: Liviana Press; New York: distributed internationally by Raven Press, 1987.
  The New England Journal of Medicine, 1988, 318: 1548. On dementia:
• L. V. Marcé:
  Recherches cliniques et anatomo-pathologiques sur la démence senile et sur les différences qui la separent de la paralysie générale.
  Gazette médicale de Paris, 1863, 34: 433-435, 467-469, 497-502, 631-632, 761-764, 797-798, 831-833, 855-858.
• A. Blumer:
  The history and use of the term dementia.
  American Journal of Insanity, Washington, 1907, 43: 337-347.
• P. Giraud:
  Evolution de l'idée de démence.
  Annales médico-psychologiques, Paris, 1943, 101: 186-199.
• W. H. McMenemey:
  Alois Alszheimer and his disease.
  In GEW Wolstenholme and M. O'Connor, editors: Alzheimer's Disease & Related Conditions. London, J & A Churchill, 1970: 5-9.
• G. E. Berrios:
  Pseudodementia or melancholic dementia: a nineteenth century view.
  Journal of Neurology, Neurosurgery and Psychiatry, London, 1995, 48: 393-400.
• R. Dillman:
  Alzheimer's Disease. The Concept of Disease and the Construction of Medical Knowledge.
  Amsterdam: Thesis Publishers, 1990.
• G. E. Berrios:
  Memory and the cognitive paradigm of dementia during the 19th century: a conceptual history.
  In: R. N. Murray, T. H. Turner, editors: Lectures on the History of Psychiatry. London: Gaskell, 1990: 194-211.

We thank Rudolf Kleinert, Bad Reichenhall, Germany, for information submitted.