A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1.

We describe a novel variant of Alzheimer's disease (AD) in a Finnish pedigree with 17 affected individuals of both sexes in three generations. The disease is characterized by progressive dementia which is, in most cases, preceded by spastic paraparesis. Neuropathological investigations revealed numerous, distinct, large, round and eosinophilic plaques as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex. The predominant plaques resembled cotton wool balls and were immunoreactive for Abeta but lacked a congophilic dense core or marked plaque-related neuritic pathology. Molecular genetic analysis revealed that the disease was caused by a deletion of exon 9 (delta9) of the presenilin 1 (PS1) gene from the mRNA: unlike previous examples of the delta9 variant, the deletion was not caused by a splice acceptor site mutation.