No association of spastic paraparesis genes in PSENI Alzheimer's disease with spastic paraparesis

Familial Alzheimer's disease due to presenilin I (PSENI) mutations shows considerable phenotypic variability with differences in neuropathology and neurological symptoms. Spastic paraparesis is a common neurological phenotype associated with Alzheimer's disease arising from PSENI mutations. To investigate whether known genes that cause spastic paraparesis could act as Alzheimer's diseasemodifier genes, we sequenced nine spastic paraparesis genes in three Alzheimer's disease families with PSENI exon 9 deletions. We did not observe any correlation of polymorphisms or mutations in the nine spastic paraparesis genes with the variable phenotype seen in families with Alzheimer's disease and spastic paraparesis. These results suggest a need for a continuing search for genes that cause the phenotypic variation in Alzheimer's disease and spastic paraparesis.