title: Neuropathological and clinical phenotype of an Italian Alzheimer family with M239V mutation of presenilin 2 gene.
abstract: Presenilin 1 and 2 are 2 highly homologous genes involved in familial Alzheimer disease. While more than 100 mutations in presenilin 1 are known to segregate with the disease in familial Alzheimer disease, only 9 mutations of presenilin 2 have been identified to date. We report the clinical and neuropathological phenotype of FLO10, the large Italian Alzheimer kindred associated with methionine to valine substitution at residue 239 of presenilin 2. The patients showed a remarkable variability in age of onset of symptoms, disease duration, and clinical presentation. The neuropathological study of 2 patients revealed peculiar features in addition to neurofibrillary changes and A beta amyloid deposits in the neuropil and vessel wall. Ectopic neurons in the subcortical white matter, often containing neurofibrillary tangles, were found in both patients, one of whom presented with epilepsy. Furthermore, 1 patient showed an unusually high number of ghost tangles in the cerebral cortex. These observations indicate that the Alzheimer kindred FLO10 associated with M239V mutation of presenilin 2 is characterized by some peculiarities of the clinical and neuropathologic phenotype compared to sporadic Alzheimer disease.
authors.affiliation: Istituto Nazionale Neurologico Carlo Besta, Milano, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Marcon
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Chiara
authors.initials: C
authors.lastname: Cupidi
authors.forename: Matteo
authors.initials: M
authors.lastname: Balestrieri
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Beltrami
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Finato
authors.forename: Paolo
authors.initials: P
authors.lastname: Bergonzi
authors.forename: Sandro
authors.initials: S
authors.lastname: Sorbi
authors.forename: Orso
authors.initials: O
authors.lastname: Bugiani
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D019943:Amino Acid Substitution; D002540:Cerebral Cortex / Q000002:abnormalities / Q000473:pathology; D002828:Choristoma / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D058225:Plaque, Amyloid / Q000473:pathology; D053766:Presenilin-2
chemical_list: D008565:Membrane Proteins; C508861:PSEN2 protein, human; D053766:Presenilin-2