Mutations in the presenilin 1 (PS1) gene (PS1) are responsible for 30%–40% of early onset familial Alzheimer's disease and over 60 mutations have been found so far. There are phenotypic variations among mutations on PS1. Three PS1 mutations, deletion of exon 9 with and without splice acceptor site mutation, and Arg278Thr have been reported to be associated with Alzheimer's disease with spastic paraparesis.1 2 We report clinical and genetic features of a man who developed very early onset Alzheimer's disease with spastic paraparesis, which was associated with a novel mutation of PS1, Phe237Ile.

A 35 year old Japanese man had graduated from a national university and had worked as a psychiatric counsellor for a local clinic. His first neurological symptom was gait disturbance at the age of 31. At the age of 32, mild memory impairment and decreased mental activity were noted. His neurological deficits progressed gradually. On neurological evaluation at the age of 33, diffuse hyperreflexia, ataxia in all limbs, bilateral Babinski's sign, and dementia (total IQ on the WAIS-R of 75) were noted. He gave up his job at this time. At the age 34, he could not live alone because of memory deficit and cognitive dysfunction (total IQ on the WAIS-R of 59). At the age of 35, he became bedridden due to deterioration of spastic paraparesis, and presented with partial or generalised seizures a few times. His parents (66 and 63 years old) and sibling (27 years old) had no neurological deficits. There was no similar disease in other members of his family. On admission, he was alert and oriented for place, but …