Characteristics of familial Alzheimer's disease in nine kindreds of Volga German ancestry

Abstract

We report the clinical and neuropathological manifestations of Alzheimer's disease (AD) in nine kindreds of German ancestry all originating from the same two adjacent villages on the West bank of the Volga River. There have been 89 known demented persons (53 male, 36 female). Mean age of onset is 57.6 +/- 8.4 years with a range of 40 to 84. Mean age at death is 66.5 +/- 7.6 years with a range of 50 to 80. Mean disease duration is 10.3 +/- 4.8 years with a range of 3 to 23. Detailed medical records were available on 50 individuals. Of these, 24% had a seizure, 72% language disturbance, 36% rigidity, 16% tremor and 12% myoclonus. There were 15 autopsies on demented persons from 6 of the kindreds. One brain suggested Creutzfeldt-Jakob disease (CJD) in a woman with the typical clinical course. The remaining 14 brains showed typical neuropathological characteristics of AD including neuritic amyloid plaques, neurofibrillary tangles, amyloid angiopathy and granulovacuolar change. Amyloid plaques were also seen in the cerebellum in all but one brain in which this region was available for review. Autopsy material from five brains in four families has been stained with antibody directed against the amyloid peptide; in all cases, the neuritic plaques stained positively. Many of the families share common surnames. It is likely that these Volga German kindreds carry the same genetic mutation leading to Alzheimer's disease; and thus, they are a valuable resource for genetic investigations of AD. Thus far, the disease in these kindreds does not show close linkage to either the D21S1 or beta amyloid gene loci on chromosome 21.