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The art of Alois Alzheimer and Gaetano Perusini

Plate 5, Fig 2,“accumulation of lipoid material in a plaque near capllary
Plate 5, Fig 2,“accumulation of lipoid material in a plaque near capllary"

Plate 19 Neuro pathology of Alzheimer's Disease drawn by Gaetano Perusini 1910Aloysius ‘Alois” Alois Alzheimer, National Library of MedicineAlzheimer (1864-1915 (Ramirez-Bermudez 2012, 595), was born 150 years ago.  He was a clinical psychiatrist and a neuropathologist best known for describing the first published case of Alzheimer’s disease. “He had a decided talent for describing lesions and profusely illustrated his works (McHenry 1969, 263).”  I consider him to be an artist as well as a scientist after seeing his illustrations in research papers by Alzheimer and his student Perusini in the Becker Medical Library.

The psychiatrist with the microscope and Auguste D.

In 1901, Auguste Deter, a 51 year old women named with increasing short-term memory loss and strange behavior, entered the Municipal Asylum of Frankfurt.  By the time she was admitted, she could not find her way around her home, dragged objects to and fro, hid herself, or sometimes thought that people were out to kill her, [and] then she would start to scream loudly.”  She often did not understand when doctors tried to examine her. Alzheimer, an experienced clinician who believed in non-restraint, was able to interview her after several tries. He followed her case closely until he moved to Munich two years later  (Alzheimer 1987, 1)

“His contemporaries called Alzheimer ‘the psychiatrist with the microscope’ because he was convinced that mental illnesses were diseases of the brain (Maurer 2003, ix).” He and Franz Nissl (of the Nissl stain) had this belief in common. Alzheimer and Nissl worked together as psychiatrists at the Municipal Asylum in Frankfurt from 1889-1896, where they saw patients during the day and spent hours at the microscope at night.

Pl. 20 Fig 2 surrounding tissue gradually transforms into the thickened plaquePlate 20, fig. 10 “Modified Neurofibryls”: from the brain of August D. PerusiniWhen Auguste Deter died in 1906, Dr. Alzheimer arranged an autopsy to preserve and study her brain. He wanted to determine what had caused the dementia which marred the last five years of her life. He arranged to have the brain and case notes sent to him in Munich where they still exist.   Using Bielshowsky's modification of the Golgi stain, he was able to fix and see under the microscope three features unusual in a woman her age. These peculiar changes Alzheimer reported to a conference of Southwest German Psychiatrists in 1906 along with clinical symptoms. However, illustrations showing the changes were published later in 1910 and 1911 by Perusini and Alzheimer.

  1. minute miliary foci (now called senile plaques) caused by deposition of a particular substance in the cortex. These plaques could be seen without staining.
  2. "the glia have developed numerous fibers; further, many glia include adipose inclusions."
  3.  "quite striking changes of the neurofibrils," which also allowed staining by dyes to which they were normally impervious, suggesting they had under gone a chemical change. (Foley 2010 , 750).

Illustrations of Alzheimer’s disease by Alzheimer and Perusini

Alois Alzheimer

Fig. 7. Peculiar fibrillary changes of the nerve cells. Eariy stage of disease. Alois Alzheimer drew beautifully what he saw of the brain under the microscope using a camera lucida attachment.  “With the camera lucida one can draw objects as they appear in nature.  The object observed through the microscope is projected onto the drawing surface through a prism.  Then one can trace the outlines of the image with a pencil and color it in.” His drawings and those of his students became the line drawings and color lithographic plates in his laboratory’s research papers. Alzheimer paid for the printing costs of the plates himself (Maurer 2003, 61). 

 

Fig. 7 by Alzheimer (1911)

Fig. 8. Peculiar fibrillary changes of the nerve cells. Progressed stage.Fig. 9 Peculiar fibrillary changes of the nerve cells. Terminal stages.Alzheimer’s drawings of the neuropathology of Alzheimer’s disease appeared in an extensive discussion of the disease in 1911 volume of the [Journal for the whole of neurology and psychiatry: originals] or Zeitschrift für die gesamte Neurologie und Psychiatrie: Originalen. Alzheimer drew the three figures 7-9 to show fibrillary changes in the nerve cells in the brain with the progression of Alzheimer’s disease. Over time, the amount of protoplasm shrinks until the neurofibrillary tangles and the occasional nucleus are shown in Figure 9, the terminal stage.

Fig. 8 by Alzheimer (1911)                                                                        Fig. 9 by Alzheimer (1911)

Plate 4, Fig. 1, fibre-forming glial cell (glz) and  a plaque (P1)Fig. 1 of Plate IV shows the relationship of the fibre-forming glial cell (glz) to a plaque (P1). In the core of the plaque a small, obviously iodine-stained, dark-brown centre, surrounded by a darker and then brighter ring. The peripheral part is traversed by extraordinarily numerous, immensely subtle glial fibrils, which originate from large glial fibres laying in the margin of the halo.

Plate 4, Fig. 2, “fibre-forming glia (glz) enclose adjacent nerve cell (gaz)In Fig. 2 of Plate IV shows, “massive fibre-forming glial cells (glz) enclosing neighbouring nerve cells (gaz) in the deeper layer of the cortex of the right upper parietal lobe (Alzheimer and Förstl, Über eigenartige Krankheitsfälle des späteren Alters (1911) (On certain peculiar diseases of old age) With 10 Text figures and 2 Plates 1911, 1991).

In contrast the senile plaques (P1, P2) are shown in Figure 1 of Plate IV and in Plate V. Plate V. Pl.Fig1 The glial cells in the core of the plaque glutted with lipoid granules.”focuses on the lipoid granules in the plaques. In Fig. I, the “central core of plaque is densely superseded by subtle red-coloured granules. The glial cells in the core of the plaque are glutted with lipoid granules.” In Fig.2, a “massive accumulation of lipoid material in a plaque [is] near a capillary.”  (Alzheimer and Förstl, Über eigenartige Krankheitsfälle des späteren Alters (1911) (On certain peculiar diseases of old age) With 10 Text figures and 2 Plates 1911, 1991)

Gaetano Perusini

Plate 19 Fig 21 Normal astrocyte glial cells drawn by Perusini.Gaetano Perusini (1879-1915) drew the normal tissue and neuropathology he saw in microscope slides more beautifully than his mentor Dr. Alzheimer. Examples shown here are Plates XVII and XX from [Histology and histopathology of the cerebral cortex] or Histologische und histopathologische Arbeiten über die Grosshirnrinde, 1910.  At Alzheimer’s suggestion Perusini re-examined the histology and clinical findings on four people with Alzheimer’s disease, including the first case, Auguste Deter (Perusini 1987, 1909-1910, 82, plate XVII and XX). Perusini’s plates are reprinted in Katherine Bick’s English translation of his paper published in 1987 (Perusini, Histology and clinical findings of some psychiatric diseases of older people =[Über klinisch und histologisch eigenartige psychische Erkrankungen des späteren Lebensalters]: a translation of 1987, 1909-1910).

Plate 20, fig. 10, 13, 16 “Modified Neurofibryls”: from the brain of August D.Plate 28 Fig 1a & b. Normal astrocyte glial cells drawn by Alzheimer.“Modified Neurofibryls”: from the brain of August D. are shown in Fig 10 and 13 of Plate XX (Perusini 1987, 1909-1910, plate XX).  A neurofibryl is any of the delicate interlacing threads coursing through the cytoplasm of the body of the neuron (Dorland 1988, 1128). The “Modified neurofibryls” are now called neurofibrillary tangles, which are intracellular knots of clumps of neurofibrils seen in the cerebral cortex in Alzheimer’s disease (Dorland 1988, 1662).

Plate XVII drawn by Perusini shows the main types of neurofibratory tangles in the ganglion cells of the cerebral cortex in Alzheimer’s disease. “Since cells corresponding to all the pictures presented are very frequent in each of the four cases described, it is not specified from which case the particular pictures derive.”  “Figures 12, 20, 21 and 23 show an especially entangled kind of basket made up of fibrils… In 8,12,13, 15, 16, 20, 22, no traces of protoplasm exist; only modified fibrils remain.  It is the same in 24 and 25 although the nucleus is clearly distinguished in both.” (Perusini 1987, 1909-1910, plate XVII).”

Plate 17 Types of neurofibratory tangles in the ganglion cells of the cortex.Plate XX shows plaques from the brain of Auguste D. in Fig. 2-5.  The different colors are due to different stains used. In Figure 3, the inclusions contained in the plaque are stained in part red and in part green (Perusini 1987, 1909-1910, Plate XX)

Plate 20, Fig. 2-5. Plaques from the brain of Auguste D.

Bibliography

Alzheimer, Alois. "A characteristic disease of the cerebral cortex (original title: Über eine eigenartige Erkrankung der Hirnrinde, 1907.)" In The early story of Alzheimer's disease, by Katherine L. Bick, translator , 1-4. New York: Liviana Press, distributed inter Nationally by Raven Press, 1987.

Alzheimer, Alois "Über eigenartige Krankheitsfälle des späteren Alters." Zeitschrift für die gesamte Neurologie und Psychiatrie: Originalen vol. 4 (1910-1911): 356–385.

Alzheimer, Alois, and Hans Förstl and Raymond Levy Förstl, translators. "Über eigenartige Krankheitsfälle des späteren Alters (1911) (On certain peculiar diseases of old age) With 10 Text figures and 2 Plates." Hans Förstl Historische Homepage. 1911, 1991. www2.psykl.med.tum.de/geschichte_history/Alzheimer_1912.html (accessed July 22, 2014).

Dorland, W. A. Newman 1864-1956. Dorland's Illustrated medical dictionary. Twenty-seventh edition. Philadelphia: Saunders, 1988.

Foley, Paul. "Lipids in Alzheimer's disease." Biochimica et biophysica acta, vol. 1801, no. 8 (Aug 2010 ): 750-3.

Graeber MB1, Mehraein P. "Reanalysis of the first case of Alzheimer's disease." Eur Arch Psychiatry Clin Neurosci. vol. 249 , no. Suppl 3 (1999): 10-13.

"History Module: Dr. Alois Alzheimer’s First Cases ." The brain from top to bottom. n.d. http://thebrain.mcgill.ca/flash/capsules/histoire_jaune03.html (accessed July 21, 2014).

Howey, Richard L. "Nineteenth Century British Microscopy and Natural History: Part 8." Microscopy UK/Micscape . July 2014. http://www.microscopy-uk.org.uk/mag/artaug08/rh-british8.html (accessed July 24, 2014).

Maurer, Konrad and Ulrike Maurer. Alzheimer: The Life of a Physician and the Career of a Disease. New York: Columbia University Press, 2003, 2003.

McHenry, Lawrence C. Jr. Garrison's Histoy of Neurology. Springfield, Illinois: Charles C. Thomas, 1969.

Perusini, Gaetano. "Histology and clinical findings of some psychiatric diseases of older people =[Über klinisch und histologisch eigenartige psychische Erkrankungen des späteren Lebensalters]: a translation of." In The early story of Alzheimer's disease: translation of the historical papers by Alois Alzheimer, Oskar Fischer, Francesco Bonfiglio, Emil Kraepelin, Gaetano Perusini, edited by Katherine, Luigi Amaducci, Giancarlo Pepeu Bick, translated by Katherine Bick, pages 82-128. New York: Liviana Press, distributed inter Nationally by Raven Press,, 1987, 1909-1910.

Perusini, Gaetano. "Über klinisch und histologisch eigenartige psychische Erkrankungen des späteren Lebensalter." In Histologische und histopathologische Arbeiten über die Großhirnrinde mit besonderer Berücksichtigung der pathologischen Anatomie des Geisteskranken, pages 297-358, Plates XVII-XXIII. Jena: G. Fischer, 1909-1910.

Ramirez-Bermudez, Jesus. "Alzheimer’s Disease: Critical Notes on the History of a Medical Concept; REVIEW ARTICLE." Archives of Medical Research 43 (2012): 595-599.

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