Neurogenetics (1998) 1 : 223–228 Q Springer-Verlag 1998 Original article Histopathology and APOE genotype of the first Alzheimer disease patient, Auguste D. M.B. Graeber 7 S. Kösel 7 E. Grasbon-Frodl 7 H.J. Möller 7 P. Mehraein Received: 29 December 1997 / Accepted: 15 January 1998 We would like to dedicate this paper to Dr. Kohshiro Fujisawa of Tokyo. His interest in Alois Alzheimer’s original work stimu- lated the search for brain samples from Johann F., Alzheimer’s second published case of Alzheimer disease (Neurogenetics 1: 73–80). The knowledge gained during this search proved indisp- ensable in the rediscovery of tissue sections belonging to Alz- heimer’s first patient, Auguste D. Following the suggestion of one reviewer of this paper, it was decided not to publish the last name of Auguste D. The infor- mation is kept on file in the editorial offices of Neurogenetics. M.B. Graeber (Y) 7 E. Grasbon-Frodl Molecular Neuropathology Laboratory, Department of Neuromorphology, Max Planck Institute of Neurobiology (formerly Max-Planck-Institute of Psychiatry, Basic Sciences Institute), Am Klopferspitz 18a, D-82152 Martinsried, Germany e-mail: neuropat6neuro.mpg.de, Tel.: c49-89-85783666, Fax: c49-89-89950077 S. Kösel 7 E. Grasbon-Frodl 7 P. Mehraein Molecular Neuropathology Laboratory, Institute of Neuropathology, Ludwig Maximilians University, Munich, Germany H.J. Möller Psychiatric Clinic, Ludwig Maximilians University, Munich, Germany ABSTRACT Alois Alzheimer published two papers on the disease which was named after him by Emil Kraepelin in 1910. Each of these papers contains clinical and pathological data on a patient Alzheimer had seen at the hospital. We have previously reported on the rediscovery of tis- sue sections from Alzheimer’s second published case of Alzheimer disease, Johann F., which probably gave the disease its name (Neurogenetics 1997; 1 : 73–80). Here, we describe the histopathology and APOE genotype of Alois Alzheimer’s first patient, Auguste D. As in the case of Johann F., a large number of tissue sections be- longing to Alzheimer’s laboratory, which was later headed by Spielmeyer, were found among material kept at the Institute of Neuropathology of the Univer- sity of Munich. As described by Alzheimer in his origi- nal report (Allg Zeitschr Psychiatr 1907; 64 : 146–148), there were numerous neurofibrillary tangles and many amyloid plaques, especially in the upper cortical layers of this patient. Yet, there was no microscopic evidence for vascular, i.e., arteriosclerotic, lesions. Interestingly, Alzheimer’s histological preparations did not include the hippocampus or entorhinal region. The APOE ge- notype of this patient was shown to be ε3/ε3 by PCR- based restriction enzyme analysis, indicating that muta- tional screening of the tissue is feasible. The historical importance of the case of Auguste D. lies in the fact that it marks the beginning of research into Alzheimer disease. In addition, neurofibrillary tangles were first described in this brain. Key words Alzheimer disease 7 Amyloid plaques 7 APOE gene 7 Dementia 7 Neurofibrillary tangles INTRODUCTION Following our report on the rediscovery of tissue sec- tions from Alois Alzheimer’s case Johann F. [1, 2], ef- forts were intensified to find material belonging to the first Alzheimer patient, Auguste D. [3]. The clinical notes of this case were found in Frankfurt and have been widely publicized [4, 5]. The great interest in the case of Auguste D. appears to be at least in part due to speculations that Alzheimer’s original patient might be classified as having a different, i.e., vascular, dementia [4]. In addition, the hypothesis has been put forth that Auguste D. may have been suffering from metachro- matic leukodystrophy (MLD; [6, 7]). However, these speculations seem ill-founded. In his 1907 publication summarizing the talk he gave at the 37th Meeting of the Southwest German Psychiatrists in Tübingen, Alzheim- er, in fact, notes “arteriosclerosis of the larger blood vessels” of Auguste D.’s brain [3] but Perusini, accord- ing to Simchowicz [8] reporting on the same case, states that these changes were “not considerable” (case I; [9]).