Background and purpose: We report a novel mutation in exon 8 of the presenilin 1 (PSEN1) gene (V261L) associated with early-onset autosomal dominant Alzheimer's disease and spastic paraparesis.
Methods and results: The proband was a woman who developed insidious cognitive decline with predominant memory loss and gait disorder secondary to spasticity at the age of 40. Her brother and her mother had a similar disease in the fifth decade of life. The feature of amnestic presentation with spastic paraparesis is consistent with the majority of mutations in the exon 8 of the PSEN1 1 gene.
Conclusions: Screening for PSEN1 mutations is especially likely to be productive when directed toward persons with positive family history and with age at onset of under 60.