Neuropsychological profiles of familial Alzheimer's disease associated with mutations in the presenilin 1 and amyloid precursor protein genes

Abstract

Patients with familial Alzheimer's disease and a subset known to have presenilin mutations were compared with sporadic cases on a comprehensive battery of cognitive tests. These included measures of memory, intelligence, language and perception. The three groups were very comparable, in terms of severity, on global measures of dementia. However, their profiles/patterns of cognitive impairment differed in two respects; the group with sporadic Alzheimer's disease were significantly more impaired on tests of object naming and object perception than either the group with familial Alzheimer's disease or group with familial Alzheimer's disease and presenilin mutations, yet they scored at a significantly higher level on the measure of verbal intelligence. This study provides further evidence of the heterogeneity of the disease process.

Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the presenilin–1 gene

“…Likewise in the Colombian E280A pedigree memory deficits predominated, with other impairments such as mild anomia [8]. In contrast, relative preservation of naming has been noted in M139V [51, 97,178] and L153V [79]. A subcortical pattern of neuropsychological deficits was noted in V272A [81].…”

“…Warrington et al [178] reported results from a neuropsychological battery of tests on 13 PSEN1 EOAD cases, eight with M139V, and one each with DelI83/M84, E120K, I143F, L250S, and Delta 9 (splice acceptor site mutation). This PSEN1 subgroup was noted to be significantly less impaired on tests of object naming and object perception, despite being at a significantly lower level on a measure of verbal intelligence, as compared with a group of patients with sporadic AD.…”

“…This PSEN1 subgroup was noted to be significantly less impaired on tests of object naming and object perception, despite being at a significantly lower level on a measure of verbal intelligence, as compared with a group of patients with sporadic AD. The possibility of a distinct subtype, reflecting selective vulnerability of neural substrates, was considered [178]. The lack of impairment on object perception may correlate with the paucity of PSEN1 cases reported with prominent visual agnosia.…”

Editorial Retraction (I)

“…Likewise, the clinical phenotype of Dentatorubropallidoluysian Atrophy in Japanese and European populations and that of Haw River syndrome in African Americans were disparate enough to hide the fact that these diseases were caused by the same mutation (11,12). Finally, presenilin mutations, described widely in Caucasian and Japanese patients, usually cause a dementia in which memory loss predominates (13), but in the sole reported example of a presenilin mutation occurring in an African kindred, personality changes and disinhibition were an early feature (14). In these examples, genetic background is the L E T T E R S www.sciencemag.org SCIENCE VOL 300 2 MAY 2003 common thread of the differing phenotype.…”

Different Clinical Phenotypes in Siblings with a Presenilin-1 P264L Mutation

“…Mutations of the PSEN1 gene have been identified in families with autosomal dominant forms of early-onset AD. Familial AD typically presents with early impairment of episodic memory [7]. However, certain PSEN1 mutations have been associated with atypical phenotypes including spastic paraparesis [8,9,10], speech production deficits [11], and frontal behavioral disturbances [12].…”