REMEMBERING ALZHEIMER: THE MAN, THE DISEASE, AND THE MICROSCOPE - ONE HUNDRED YEARS LATER
Manuel del Cerro (USA) and Lazaros C. Triarhou (Greece)
We all have heard about Alzheimer’s disease. That progressive, devastating disease characterized mainly by a relentless memory loss, was initially brought to the attention of the medical community one hundred years ago. At a meeting of the South-West German Society of Alienists in November 1906 Alzheimer (Alzheimer, 1906) described "eine eigenartige Erkrankung der Hirnrinde" (a peculiar disease of the cerebral cortex) [Fig 1].
Figure 1. A popular photograph of Professor Alois Alzheimer.
Microscopic analysis of affected brains by Prof. Alzheimer (1864-1915) lead to the discovery of lesions that are the hallmark of the disease, the plaques and the neurofibrillary tangles [Fig. 2].
Figure 2. Microscopic alterations of brain tissue affected by Alzheimer disease. A plaque is shown in the center of the field (asterisk) as a round mass formed by heterogeneous material. Neurons with fibrillary tangles in their cell bodies appear as dense, inverted triangles on the left and right sides of the picture (arrowheads).
Controversy continues to this day about the respective roles of microscopic changes, and whether or not they are cause or effect of the basic pathological process. The details of that controversy are outside the realm of this brief commemorative note. Information about the disease is plentiful in the medical literature and easily obtained from even the most cursory exploration of the web. Also, several biographies of Alzheimer have been published, (ex. Lewey, 1970, Beighton & Beighton, 1986), and many are available on-line. Here we will explore the question of what microscopic equipment was used one hundred years ago by Prof. Alzheimer, the chain cigar-smoking psychiatrist-clinical researcher who was fond of “spending evenings and nights at the microscope.” (www.whonamedit.com, 2006).
There are two original Alzheimer papers from 1892 and 1897 from his Frankfurt years (Alzheimer 1892; Alzheimer 1897), dealing with a progressive spinal muscle atrophy and colloid degeneration, where he does mention using Zeiss: "homog. immers. 1/12, compens. ocular 4 or 2", "Zeiss Obj. A Ocular 2", "Homog. Immersion 1.3, and Compensationsocular 4", "Zeiss Objectiv DD, Ocular 4". That is, he was using Zeiss oculars and oil immersion objectives. He, most likely, mounted them on a Zeiss stand. That brings the question of, what was the best research stand made by Zeiss towards the end of the 19th century and the first decade of the 20th? The answer is known, by 1898 Zeiss had introduced what was called the large research stand of the jug-handle type – a superb instrument [fig.3]. Although indirect, the available evidence is suggestive that this was the microscope model that allowed one of the most important discoveries in brain pathology made in the 20th century, one that still has relevance today.
Figure 3. A Zeiss Jug-handle stand as the one likely used by Professor Alzheimer for his 1906 study on the disease that now carries his name. This was a state-of-the-art model manufactured from approximately 1898 to 1910. Instrument from the collection of one of the authors (MdC). This instrument too, is fitted with compensator oculars and it carries, among others, a 1/12 NA 1,30 oil immersion objective, that is to say, the optical components that were mounted on Alzheimer’s microscope.
Alzheimer, A. (1906) Über einen eigenartigen schweren Erkrankungsprozeί der Hirnrinde. Neurol. Centralbl. (Leipz.) 25: 1134.
Alzheimer, A. (1892) Über einen Fall von spinaler progressiver Muskelatrophie mit hinzutretender Erkrankung bulbδrer Kerne und der Rinde. Arch. Psychiat. Nervenkrankh. 23: 459-485.
Alzheimer, A. (1897) Die Colloidentartung des Gehirns. Arch. Psychiat. Nervenkrankh. 30: 18-53.
Beighton, P. & Beighton, G. (1986) The Man Behind the Syndrome. Springer Verlag, Berlin, pp. 8-9.
Lewey, F.H. (1970) Alois Alzheimer (1864-1915), in Web Haymaker and Francis Schiller, The Founders of Neurology, pp. 315-319.
Møller, H.-J & Graeber, M.B. (1998) The case described by Alois Alzheimer in 1911: Historical and conceptual perspectives based on the clinical record and neurohistological sections. Eur. Arch. Psychiat. Clin. Neurosci. 248: 111-122.
Stelzmann, R.A., Schnitzlein H.N. & Murtagh, R.F. (1995) An English Translation of Alzheimer’s 1907 Paper, “Über eine eigenartige Erkrankung der Hirnrinde”. Clin. Anat. 8: 429-431.
Comments and criticism to the authors are most welcome.
Published in the September 2006 edition of Micscape.
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