Clinical characterization of an APP mutation (V717I) in five Han Chinese families with early-onset Alzheimer's disease

The missense mutation V717I in amyloid precursor protein (APP) gene has been reported in many early-onset familial Alzheimer's disease (EOFAD) families. However, no detailed clinical picture regarding this mutation has ever been described for Chinese EOFAD. We investigate the age at onset (AAO), initial clinical features and non-cognitive neurological symptoms in 34 affected subjects from five Han Chinese EOFAD families with the APPV717I mutation to characterize the clinical phenotype. The AAO was 54.7 ± 4.9 years (n = 34), with the APOE ɛ4 allele correlating with a decreased AAO. Prominent early affective symptoms, executive dysfunction and disorientation at onset were exhibited in 26 (76.5%), 18 (52.9%) and 16 (47%) cases, respectively. Spastic paraparesis and cerebellar ataxia occurred frequently in 13 (38.2%) and 12 (35.3%) cases, respectively, during the late stages of disease. The specific clinical phenotype of the APPV717I mutation for Chinese families is characterized by prominent early affective symptoms, executive dysfunction and disorientation as well as frequent late spastic paraparesis and cerebellar ataxia as compared to Western reports. We conclude that ethnic differences, environment or additional unknown factors may challenge the homogeneity of EOFAD with identical APP mutations.