ABSTRACT
We describe the kindred of Alois Alzheimer's second published patient (Johann F.) with the brain pathology typical of a subgroup of Alzheimer disease called "plaque-only type." The genealogic records of the kindred extend back to 1670. We constructed a family tree of 1403 individuals and identified 4 living demented members of the Johann F. kindred. The pedigree is consistent with an autosomal dominant trait. The analyses of known dominant dementia genes (APP, PS1, PS2, PRNP, and BRI) failed to reveal mutations in the proband. Further examination of this family might yield new insights into the genetics of Alzheimer disease.
Subject(s)
Alzheimer Disease/genetics , Alzheimer Disease/pathology , Brain/pathology , Plaque, Amyloid/pathology , Adaptor Proteins, Signal Transducing , Aged , Aged, 80 and over , Amyloid/genetics , Amyloid beta-Protein Precursor/genetics , DNA Mutational Analysis , Female , Humans , Male , Membrane Glycoproteins , Membrane Proteins , Pedigree , Presenilin-1/genetics , Presenilin-2/genetics , Prion Proteins , Prions/genetics , Protease Nexins , Receptors, Cell Surface/geneticsABSTRACT
Alois Alzheimer evaluated five cases of Alzheimer's disease in the early 20th century. We focused on the family of "Johann F.," Alzheimer's second patient, who died in October 1910 at age 57 years, and whose brain pathology is typical of a subgroup of Alzheimer's disease, the so-called "plaque-only type." It was perhaps Emil Kraepelin's personal knowledge of this patient and the histological data of the other four cases that influenced Kraepelin to coin the term Alzheimer's disease. The church archive in Passau has a genealogical database drawn from sacramental registers dating from approximately 1580 to 1900. The genealogical data of the "Johann F." family, which comes from villages in Lower Bavaria, extends as far back as 1670. We found documentation starting around 1830 about cause of death in the church records, which shows a familial predisposition to dementia. Affected family members include the mother, maternal grandfather, maternal great-aunt, maternal great-grandfather as well as three of Johann F.'s eight siblings. The offspring (children and grandchildren) of these affected siblings also were affected by mental illness. We conclude that "Johann F." represents the index case of a family with a predisposition to presenile dementia with variable age of onset (30s to 60s).
