Whilst the name of Alois Alzheimer (1864-1915) is familiar to every neurologist, if not every schoolboy, and the 100th anniversary of his seminal publications [1,2] on the disease which came to bear his name, courtesy of Kraepelin’s systematising, attracted much attention [3-5], it is unlikely that the name of Dr Solomon Carter Fuller (Figure 1) will be known to any but a handful of Alzheimer’s disease (AD) cognoscenti. This obscurity prevails despite the fact that Fuller published what was probably the first paper on AD to appear in the English language.

Fuller’s distinguished biography, beginning in Liberia as the grandson of a freed slave and culminating as the first African-American to practice as a psychiatrist in the United States of America, for many years at the Westborough Insane Hospital and at Boston University School of Medicine, has been well documented [6-8]. He was granted leave of absence from his post at Westborough for postgraduate studies with Emil Kraepelin (1856-1926) in Munich for two semesters in 1904-5, and here he was one of only five ‘privalesmus’ admitted to the course run by Alzheimer, his acceptance perhaps facilitated by his prior experience in histology and his working knowledge of the German language [8].

Little is known about Fuller’s work in Alzheimer’s laboratory, for example, it is not clear if he knew of ‘Alzheimer’s first case’, Auguste D. Nevertheless, it is evident from his subsequent work that Fuller took an interest in Alzheimer’s publications, not surprisingly. The purpose of this article is to look again at Fuller’s major publications related to AD and its pathology [9-12] which appeared in the American Journal of Insanity and the Journal of Nervous and Mental Disease between 1907 and 1912.

Fuller’s 1907 American Journal of Insanity paper [9] was a histological study of neurofibrils in various conditions, including three cases of ‘dementia senilis’ as well as cases of dementia paralytica and chronic alcoholism, using the Bielschowsky silver impregnation method. At the outset (416), Fuller acknowledged his “indebtedness to Prof. Kraepelin for his kind permission to use the facilities of the Munich Psychiatric Clinic, where most of our preliminary work was done, and also to Dr Alzheimer, of the same institution, under whose direction we began the study of the neurofibrils”. The three patients reported (cases VIII, IX, and X; 444-447) were all elderly males (8th decade). Macroscopic atrophy of the cerebral convolutions was noted in two cases. Diffuse alterations in neurofibrils in the cerebral cortex were noted in all cases: “The cells present a somewhat shrunken appearance and fragmentation, granulation and disappearance of the fibrils are common” (447). Fuller concluded that “diffuse destruction of intercellular [sic] fibrils … is the rule in dementia senilis” (460) and that silver impregnation for neurofibrils might be used to differentiate dementia paralytica “from a disease with a dystrophic substratum such as dementia senilis” (461).

There is no account or illustration (Figures 16 and 21, not 20 as reported in text) which resembles or could be recognised as the neurofibrillary tangle which had been delineated by Alzheimer in his first case, and no mention of Alzheimer’s first papers [1,2]. It may be that at this time Fuller was not aware of these publications. In his 1912 paper (in two parts) in the Journal of Nervous and Mental Disease [10,11], Fuller used the term Alzheimer’s disease, acknowledging: “The first published case presenting the combination of clinical and microscopical changes discussed in this paper was reported by Alzheimer in 1906” (440). Fuller cited Alzheimer’s 1907 paper [2] (incorrectly as 1906) and included a translation of this case (452-454), as well as material from 11 other papers in the literature reporting similar cases, including Alzheimer’s 1911 publication (541-543), the ‘second case’ of Johann F [13,14]. Fuller’s patient was a man in his 50s with symptoms which, with hindsight, seem consistent with amnesia, aphasia without anomia, apraxia and possibly agnosia. At autopsy, he was noted to have “regional atrophies of cerebrum” (444). With the Bielschowsky method “easily the most characteristic findings are the presence of a great number of plaques” (448) which are illustrated (Figures 1, 2, and 4, the latter with surrounding neuritic change, described as “Alzheimer degeneration”, 449). Furthermore, “many ganglion cells … exhibit the Alzheimer type of degeneration. This degeneration consists of a tangled mass of thick, darkly staining snarls and whirls of the intracellular fibrils” (451), the illustration of which (Figure 3, 448) is typical of neurofibrillary tangles. Glial proliferation was also reported (454). Of note, Fuller used the term “senium praecox” for this case (which he believed to be the 8th recorded case of Alzheimer’s disease [12]) and the other cases from the literature which he reviewed, this term apparently synonymous with ‘Alzheimer’s disease’ (440, 452), presumably to distinguish these cases from ‘dementia senilis’.

Some fifty years later, Allison [15] claimed that in this paper Fuller noted convulsive fits in a confirmed case of Alzheimer’s disease in the later stages, if so a most interesting observation in view of current interest in the occurrence of epileptic seizures in AD [16,17]. Reading Fuller’s lengthy case report [10], I can only presume that Allison refers to the “short periods of unconsciousness or dream-like states” which occurred in the two years before the patient’s ‘final breakdown’ (441), but no account of convulsion has been found. However, in his summary of previously published cases [11], Fuller noted that “In a few of the cases motor disturbances have been noted as residua of epileptiform convulsions. Convulsions with loss of consciousness, however, have not been observed, save in the terminal stage, epileptiform attacks and muscular twitchings being recorded” (554). It is now well-recognised that epileptic seizures and myoclonus become more evident with progression of AD [16]. In Fuller’s review, most patients showed evidence of brain atrophy, either general or regional, all but one had evidence of plaques, and all but one had “peculiar basket-like alterations due to the presence of thick, darkly staining intracellular fibrils arranged in whorls or in a tangled mass” (555), the exception being Alzheimer’s second case [13].

With his colleague Henry Klopp, Fuller reported in the American Journal of Insanity in 1912 a second personally examined case believed to be an example of Alzheimer’s disease [12]. This judgement was based on the clinical history and autopsy findings of plaques but “the Alzheimer degeneration of intracellular neurofibrils … was not exhibited” [24], as in Alzheimer’s second case [13] and differing from the first Westborough case [10]. The nosological position of “Alzheimer’s disease” vis-a-vis senile dementia was discussed, the former being conceived of as an “atypical form of senile dementia” [26].

Fuller’s diligence, industry, and skill are readily apparent from his papers. Evidently, he was in the right place at the right time and possessed the right skills to contribute to the contemporaneous debate on the new diagnostic entity of Alzheimer’s disease. In retrospect, it is puzzling that he reported nothing resembling neurofibrillary tangles in the brains of patients with “dementia senilis” in his 1907 paper. One may surmise that his views evolved between 1906 and 1912, perhaps as a result of his ongoing studies and his reading of Alzheimer’s papers [1,2,13]. Fuller’s position as a pioneer of Alzheimer’s disease studies in the English language is unquestionable and he deserves to be more widely known.

References
  1. Alzheimer A. Über den Abbau des Nervengewebes. Centralblatt fur Nervenheilkunde und Psychiatrie 1906;29:526-8.
  2. Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift fur Psychiatrie und Psychisch-Gerichtlich Medizine 1907;64:146-8.
  3. Hodges JR. Alzheimer’s centennial legacy: origins, landmarks and the current status of knowledge concerning cognitive aspects. Brain 2006;129:2811-2822. https://doi.org/10.1093/brain/awl275
  4. Perry G, Avila J, Kinoshita J, Smith M (eds.). Alzheimer’s disease. A century of scientific and clinical research. Amsterdam: IOS Press, 2006. https://doi.org/10.3233/JAD-2006-9S301
  5. Larner AJ. Alzheimer 100. Adv Clin Neurosci Rehabil 2006;6(5):24.
  6. Cobb WM. Solomon Carter Fuller, 1872-1953. J Natl Med Assoc 1954;46:370-2.
  7. Kaplan M, Henderson AR. Solomon Carter Fuller, M.D. (1872-1953): American pioneer in Alzheimer’s disease research. J Hist Neurosci 2000;9:250-61. https://doi.org/10.1076/jhin.9.3.250.1792
  8. Kaplan M. Solomon Carter Fuller. Where my caravan has rested. Lanham: University Press of America, 2005.
  9. Fuller SC. A study of the neurofibrils in dementia paralytica, dementia senilis, chronic alcoholism, cerebral lues and microcephalic idiocy. Am J Insanity 1907;63:415-68. https://doi.org/10.1176/ajp.63.4.415
  10. Fuller SC. Alzheimer’s disease (senium praecox): the report of a case and review of published cases. J Nerv Ment Dis 1912;39:440-55. https://doi.org/10.1097/00005053-191207000-00002
  11. Fuller SC. Alzheimer’s disease (senium praecox): the report of a case and review of published cases. J Nerv Ment Dis 1912;39:536-57. https://doi.org/10.1097/00005053-191208000-00002
  12. Fuller SC, Klopp HI. Further observations on Alzheimer’s disease. Am J Insanity 1912;69:17-29.
  13. Alzheimer A. Über eigenartige Krankheitsfalle des spateren Alters. Zeitschrift fur die gesamte Neurologie und Psychiatrie 1911;4:356-85. https://doi.org/10.1007/BF02866241
  14. Klünemann HH, Fronhöfer W, Wurster H, Fischer W, Ibach B, Klein HE. Alzheimer’s second patient: Johann F. and his family. Ann Neurol 2002;52:520-3. https://doi.org/10.1002/ana.10309
  15. Allison RS. The senile brain. A clinical study. London: Edward Arnold, 1962:118.
  16. Larner AJ. Epileptic seizures in AD patients. Neuromolecular Med 2010;12:71-7. https://doi.org/10.1007/s12017-009-8076-z
  17. Friedman D, Honig LS, Scarmeas N. Seizures and epilepsy in Alzheimer’s disease. CNS Neurosci Ther 2012;18:285-94. https://doi.org/10.1111/j.1755-5949.2011.00251.x

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