Angela R.: a familial Alzheimer’s disease case in the days of Auguste D.

Abstract

The rebuilding of the N family, a large Italian kindred affected by early-onset autosomal dominant Alzheimer’s disease (AD), provided an important contribution to the discovery of Presenilin 1 (PSEN1), the main gene responsible for familial AD. This pedigree was identified with the help of medical records from the archives of the Psychiatric Hospital of Girifalco, Italy. The clinical record of Angela R., an ancestor of the N family, dating back to 1904, showed a clinical picture of Angela R., consistent with a diagnosis of non-amnestic probable AD, matching the “dysexecutive” phenotype described in her descendants. The a posteriori diagnosis of AD is supported by the evidence of the causative genetic mutation PSEN1-Met146Leu as well as neuropathological AD features in her genealogically proven descendants. The clinical case of Angela R. was recorded at the same time of Alzheimer’s description of Auguste D. Its discovery crucially contributed to the genealogical reconstruction of the N family, linking came from different branches, which until then were unrelated, to the same kindred. The archives of the Girifalco Hospital represented a valuable source of medical and historical information and were essential to the research on Italian-American AD families that finally led to the identification of new genes.