Author Affiliations: Geriatrics Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System (Drs Bird and Yu); and Department of Neurology, University of Washington (Dr Bird), Seattle.
Auguste D. is one of the best known patients in the history of medicine and neurology. The detailed clinical and pathological examination of this patient by Alois Alzheimer in 1906 and 1907 began the cascade of events that has become the international investigation of Alzheimer disease. Our hypothesis that Auguste D. had the N141I mutation in the presenilin-2 (PSEN2) gene was of historical and genetic interest and, most importantly, testable.1 This hypothesis has now been disproven. Auguste D. did not have the N141I mutation in PSEN2. We thank Dr Müller and colleagues for their careful molecular analysis of this valuable tissue. The etiology and biological pathogenesis initiating the early onset of neuritic plaques and neurofibrillary tangles in Auguste D. remains a mystery today, just as it was for Alzheimer more than 100 years ago.
Bird TD, Yu C. Alois Alzheimer's Case, Auguste D., Did Not Carry the N141I Mutation in PSEN2 Characteristic of Alzheimer Disease in Volga Germans—Reply. Arch Neurol. 2011;68(9):1210-1211. doi:10.1001/archneurol.2011.219