Introduction

One hundred years ago, in January of 1907, Alois Alzheimer published his landmark paper about Auguste D. This is a perfect time to sit back and contemplate the field’s past accomplishments and future challenges. The Alzforum editors have compiled some materials to jumpstart your mind on this journey. Enjoy the offerings of this Centennial Page, and write back with your comments.

How far have a hundred years brought us in understanding Alzheimer disease? Alzforum advisory board member Michael Schlossmacher proposed that we focus attention on what we still do not know. With the help of our scientific advisory board, we have attempted to compile a list both of the field’s achievements and the great unknowns. We invite you to review this list, share your observations and comments, and help shape a research agenda for the future of AD research. You can comment on each statement-question pair simply by clicking on the Submit Comment button.

Background

Background Text
By Gabrielle Strobel

The end of 2006 saw the AD100 Centennial conference in Tuebingen, held on the very day 100 years earlier, and in the same building, where Alois Alzheimer first presented his description of the disease to a decidedly unimpressed audience of fellow psychiatrists. This event is captured in Gabrielle Strobel’s conference report, and her biographical story about the man behind the eponym. Enjoy our photo gallery of conventioneers and other images to put faces to the names of Alzheimerologists you’ve been reading about for years. Make sure to read Jennifer Altman's summary of the scientific talks from the AD100 Centennial conference in Tuebingen. It doubles as a wonderfully concise history of the field. (We thank the IPSEN Foundation for giving permission to post the English version of Jennifer Altman’s report.) An anthology of chapters by the presenters is available from Springer, including a chapter about the origins of the Alzforum.

A special treat for people interested in Alois Alzheimer is a book by his two historians, Konrad Maurer and his wife Ulrike. A psychiatrist himself, Maurer directs the Clinic for Psychiatry and Psychotherapy at the University of Frankfurt, and his wife has restored Alzheimer's birth house into a museum and unique meeting venue. To help us celebrate this historic point in time, the authors have generously granted the Alzforum permission to post selected images from their book Alois Alzheimer, His Life and Work with Text and Photographs (2002, Pre-Press Print Production Service and Verlag, Marburg Germany, ISBN 3-935966-05-09) [View slideshow]. The book contains much more information than is highlighted here, for example, original records of Alzheimer's extensive examinations of Auguste D., which document his skill as a clinician and her despair and decline. On behalf of the Alzheimer research community, we express our warmest gratitude.

Lest anyone believe Alzheimer’s contribution was made in a scientific vacuum, ponder Andre Delacourte’s historic perspective. Delacourte has dug up papers predating Alzheimer’s own report of Auguste D’s case, and he has posted excerpts of those old papers on his website for all to enjoy. Delacourte’s comment shows how Alzheimer melded bits and pieces of previous knowledge by other international workers with his own painstaking clinico-pathological observations into a cohesive description of this disease.

A broad review of scientific and clinical research since 1906 is available from IOS Press. Edited by George Perry, Jesus Avila, June Kinoshita, and Mark Smith, this 450-page tome features a diverse set of chapters written by old and new hands of AD research, as well as by lesser known writers who offer new perspectives.

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Comments on this content

  1. Alzheimer—The Great Assimilator? Let’s Recall Other Early Workers
    On this occasion I’d like to contribute some historical notes on Alzheimer disease to encourage the field to recognize previous work that prepared Alzheimer’s mind. I welcome comments and other perspectives. Undoubtedly, Alois Alzheimer made a great contribution in painstakingly assembling and describing this disease clinically and pathologically. This leap occurred at different levels: Alzheimer provided a good description of neurofibrillary degeneration using Bielchowski staining; he demonstrated that plaques and neurofibrillary degeneration can be found in presenile cases; and he offered an anatomical-neuropathological description of a presenile case of dementia strongly suggesting a link between these brain lesions (plaques and tangles) and dementia. However, he did not actually discover anything truly new, nor did he ever claim to have done so. All the markers that Alzheimer reported were known at the time, and it is clear from his writings that he never meant to say they were new.

    For example, Beljahow in 1889 (Beljahow S: Pathological changes in the brain in dementia senilis. Journal of Mental Science 1889; 35:261–262) reported that in senile dementia, nerve cells and their extensions were abnormal. He noted pathological alterations, cells being broken down into formless clumps. Beljahow mentioned that a process of “general degeneration” was observed in senile dementia. In 1892, the French pathologist Paul Oscar Blocq and the Romanian neurologist Georges Marinesco described plaques and noted the size of some as being 60 microns; however, their paper refers to this pathology exclusively in the context of epilepsy, not dementia (Blocq, Marinesco, 1892). I have translated this paper for the enjoyment of the Alzheimer Research Forum community. The link between plaques and dementia was clearly discussed by Emil Redlich in 1898, and then by Andre Leri in 1906. The poorly known Czech researcher, Oskar Fischer, pointed out in 1907 (the same year as Alois Alzheimer’s publication of Auguste D’s case) that “miliary necrosis” should be considered a marker of senile dementia. He described with great precision “neuritic plaques” that are the most specific lesions of AD, and some of his drawings can be admired at http://www.alzheimer-adna.com/Gb/History/Fischer.html. For a further historic account of the concept of Alzheimer’s disease, see German Berrios’s online article.

    References:

    . Sur les lesions et la pathogenie de l'epilepsie dite essentiale. Semaine medicale. 1892 Jan;12:445-6.

  2. These new contributions to the history of Alzheimer disease further illuminate the setting in which Alzheimer made his original observations. I look forward to reading the issue coming out of the Tubingen conference.

    Many thanks to Andre Delacourte for his comments and his posted translation of Blocq and Marinesco’s paper. These translations by European authors are extremely valuable to North Americans like myself, who speak only one language. Commercial translations are generally so costly as to be prohibitive.

    I would also like to alert those interested in the history of Alzheimer disease to my own paper [1], which summarized the research (mostly the English-language literature) in the time between Alzheimer’s initial paper up to the cholinergic hypothesis of the 1970s. A focus of this paper is the debates surrounding whether AD was caused by cerebral atherosclerosis, whether it differed from normal aging, and whether it was a separate disease or just earlier onset senile dementia (of the AD type).

    Also, I would direct readers to Zaven Khachaturian’s recent paper [2], in which Zaven recounts the politics behind the efforts of the National Institute on Aging to advance AD research.

    References:

    . The history of Alzheimer's disease: three debates. J Hist Med Allied Sci. 1987 Jul;42(3):327-49. PubMed.

    . History of Alzheimer's research: the politics of science in building a national program of research. Alzheimer Dis Assoc Disord. 2006 Jul-Sep;20(3 Suppl 2):S31-4. PubMed.

  3. I would like to bring everyone's attention to what could be a seminal paper on AD: <a href="/papers/biochemical-study-etiology-alzheimers-disease">Imahori, 2010</a>. In it, the author lays out that tau is heavily phosphorylated by tau protein kinase 1 and 2, which also phosphorylate pyruvate dehydrogenase, inactivating it. That inactivation causes cell death—the mitochondria, lights out.

    <p>TPKI is upregulated in the AD brain, and can be upregulated by a specific form of Aβ, a spherical oligomer of about 10-15 nm. The other forms of Aβ were not bioactive in his tests.

    </p><p>It is the identification of this specific spherical oligomer of Aβ that is most exciting.

    References:

    . The biochemical study on the etiology of Alzheimer's disease. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(1):54-61. PubMed.

References

News Citations

  1. Tuebingen: Researchers Reminisce, Predict at Alzheimer Centennial
  2. Tuebingen: The Man Behind the Eponym
  3. Alzheimer: 100 Years and Beyond

Paper Citations

  1. . Über eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift fur Psychiatrie und Psychisch-gerichtliche Medizin. 1907 Jan;64:146-8.

Other Citations

  1. View slideshow

External Citations

  1. Springer
  2. IOS Press

Further Reading

Papers

  1. . The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein. Nature. 1999 Jun 24;399(6738):784-8. PubMed.