A VARIANT OF ALZHEIMERS-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 p edigree with 17 affected individuals of both sexes in three generation s. The disease is characterized by progressive dementia which is, in m ost cases, preceded by spastic paraparesis. Neuropathological investig ations revealed numerous, distinct, large, round and eosinophilic plaq ues as well as neurofibrillary tangles and amyloid angiopathy througho ut the cerebral cortex. The predominant plaques resembled cotton wool balls and were immunoreactive for AP but lacked a congophilic dense co re or marked plaque-related neuritic pathology. Molecular genetic anal ysis revealed that the disease was caused by a deletion of exon 9 (Del ta 9) of the presenilin 1 (PSI) gene from the mRNA: unlike previous ex amples of the Delta 9 variant, the deletion was not caused by a splice acceptor site mutation.