title: Interfamilial and intrafamilial phenotypic heterogeneity in familial Alzheimer's disease.
abstract: The features of Alzheimer's disease (AD) are very heterogenous, and some component of the variability of AD is likely to be related to genetic factors. To investigate this question, we evaluated 19 clinical neuropsychiatric and brain imaging features in 32 familial Alzheimer's disease (FAD) kindred, primarily of late onset. Within families, patients displayed a high degree of phenotypic heterogeneity (PH), which occurred irrespective of gender, ethnicity, or apolipoprotein E genotype. Overall, an equivalent amount of PH was observed in both the between- (37%) and within-family (31%) groups. However, for onset age and rate of decline between families, there was greater PH than within families (P = .002 and P = .01, respectively). A similar trend was found for severity of cortical atrophy (P = .05). These observations suggest a weak genetic influence, and possibly strong nongenetic influences, on the degree of phenotypic heterogeneity in late-onset FAD. In early-onset AD kindred, a much smaller degree of phenotypic heterogeneity may be expected within families, because genetic influences in phenotypic expression tend to be more prominent in early-onset cases.
authors.affiliation: Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Florida 33140, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Lopez-Alberola
authors.forename: W W
authors.initials: WW
authors.lastname: Barker
authors.forename: D G
authors.initials: DG
authors.lastname: Harwood
authors.forename: D A
authors.initials: DA
authors.lastname: Loewenstein
authors.forename: P H
authors.initials: PH
authors.lastname: George-Hyslop
authors.forename: T
authors.initials: T
authors.lastname: Tsuda
authors.forename: E A
authors.initials: EA
authors.lastname: Rogaeva
authors.forename: R
authors.initials: R
authors.lastname: Duara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy; D002540:Cerebral Cortex / Q000473:pathology; D005190:Family; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010641:Phenotype
chemical_list: D001057:Apolipoproteins E