title: A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1.
abstract: 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.
authors.affiliation: Mayo Clinic Jacksonville, Florida 32084, USA.
authors.forename: R
authors.initials: R
authors.lastname: Crook
authors.forename: A
authors.initials: A
authors.lastname: Verkkoniemi
authors.forename: J
authors.initials: J
authors.lastname: Perez-Tur
authors.forename: N
authors.initials: N
authors.lastname: Mehta
authors.forename: M
authors.initials: M
authors.lastname: Baker
authors.forename: H
authors.initials: H
authors.lastname: Houlden
authors.forename: M
authors.initials: M
authors.lastname: Farrer
authors.forename: M
authors.initials: M
authors.lastname: Hutton
authors.forename: S
authors.initials: S
authors.lastname: Lincoln
authors.forename: J
authors.initials: J
authors.lastname: Hardy
authors.forename: K
authors.initials: K
authors.lastname: Gwinn
authors.forename: M
authors.initials: M
authors.lastname: Somer
authors.forename: A
authors.initials: A
authors.lastname: Paetau
authors.forename: H
authors.initials: H
authors.lastname: Kalimo
authors.forename: R
authors.initials: R
authors.lastname: Ylikoski
authors.forename: M
authors.initials: M
authors.lastname: Pöyhönen
authors.forename: S
authors.initials: S
authors.lastname: Kucera
authors.forename: M
authors.initials: M
authors.lastname: Haltia
mesh_terms: D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology*; D005091:Exons; D005260:Female; D005387:Finland; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D010375:Pedigree; D058225:Plaque, Amyloid / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D053764:Presenilin-1; D012333:RNA, Messenger / Q000096:biosynthesis; D017384:Sequence Deletion; D015419:Spastic Paraplegia, Hereditary / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012333:RNA, Messenger