Clinical characteristics in a kindred with early-onset alzheimer’s disease and their linkage to a g→t change at position 2149 of the amyloid precursor protein gene

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Abstract

Patients from five generations of a family developed presenile Alzheimer's disease (AD) early in the fifth decade. Recent memory, information-processing speed, sequential tracking, and conceptual reasoning were the earliest cognitive functions affected. Language and visuoperceptual skills were largely spared early in the course of the disease. Later, there were progressive cognitive deficits and inability to perform the activities of daily living. Death occurred, on average, 6 years after onset. Three autopsies in affected members revealed cerebral amyloid deposits and neurofibrillary tangles. Clinical and pathologic features were typical for familial AD. Direct DNA sequencing revealed a G→T change at position 2149 of the amyloid precursor protein (APP) gene that resulted in the substitution of phenylalanine for valine in the transmembrane domain of the mature protein. This mutation was present in DNA from all four examined affected individuals and linked to the disease with a lod score of 3.25, and was the most probable cause of AD in this family.

Original languageEnglish
Pages (from-to)105-111
Number of pages7
JournalNeurology
Volume44
Issue number1
StatePublished - 1994

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Amyloid beta-Protein Precursor
Alzheimer Disease
Genes
Lod Score
Neurofibrillary Tangles
Amyloid Plaques
Valine
Activities of Daily Living
Phenylalanine
DNA Sequence Analysis
Automatic Data Processing
Cognition
Autopsy
Language
Mutation
DNA
Onset
Gene
Linkage
Alzheimer's Disease

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology
  • Neuroscience(all)

Cite this

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title = "Clinical characteristics in a kindred with early-onset alzheimer’s disease and their linkage to a g→t change at position 2149 of the amyloid precursor protein gene",
abstract = "Patients from five generations of a family developed presenile Alzheimer's disease (AD) early in the fifth decade. Recent memory, information-processing speed, sequential tracking, and conceptual reasoning were the earliest cognitive functions affected. Language and visuoperceptual skills were largely spared early in the course of the disease. Later, there were progressive cognitive deficits and inability to perform the activities of daily living. Death occurred, on average, 6 years after onset. Three autopsies in affected members revealed cerebral amyloid deposits and neurofibrillary tangles. Clinical and pathologic features were typical for familial AD. Direct DNA sequencing revealed a G→T change at position 2149 of the amyloid precursor protein (APP) gene that resulted in the substitution of phenylalanine for valine in the transmembrane domain of the mature protein. This mutation was present in DNA from all four examined affected individuals and linked to the disease with a lod score of 3.25, and was the most probable cause of AD in this family.",
author = "Martin Farlow and J. Murrell and Bernardino Ghetti and Frederick Unverzagt and S. Zeldenrust and Merrill Benson",
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T1 - Clinical characteristics in a kindred with early-onset alzheimer’s disease and their linkage to a g→t change at position 2149 of the amyloid precursor protein gene

AU - Farlow, Martin

AU - Murrell, J.

AU - Ghetti, Bernardino

AU - Unverzagt, Frederick

AU - Zeldenrust, S.

AU - Benson, Merrill

PY - 1994

Y1 - 1994

N2 - Patients from five generations of a family developed presenile Alzheimer's disease (AD) early in the fifth decade. Recent memory, information-processing speed, sequential tracking, and conceptual reasoning were the earliest cognitive functions affected. Language and visuoperceptual skills were largely spared early in the course of the disease. Later, there were progressive cognitive deficits and inability to perform the activities of daily living. Death occurred, on average, 6 years after onset. Three autopsies in affected members revealed cerebral amyloid deposits and neurofibrillary tangles. Clinical and pathologic features were typical for familial AD. Direct DNA sequencing revealed a G→T change at position 2149 of the amyloid precursor protein (APP) gene that resulted in the substitution of phenylalanine for valine in the transmembrane domain of the mature protein. This mutation was present in DNA from all four examined affected individuals and linked to the disease with a lod score of 3.25, and was the most probable cause of AD in this family.

AB - Patients from five generations of a family developed presenile Alzheimer's disease (AD) early in the fifth decade. Recent memory, information-processing speed, sequential tracking, and conceptual reasoning were the earliest cognitive functions affected. Language and visuoperceptual skills were largely spared early in the course of the disease. Later, there were progressive cognitive deficits and inability to perform the activities of daily living. Death occurred, on average, 6 years after onset. Three autopsies in affected members revealed cerebral amyloid deposits and neurofibrillary tangles. Clinical and pathologic features were typical for familial AD. Direct DNA sequencing revealed a G→T change at position 2149 of the amyloid precursor protein (APP) gene that resulted in the substitution of phenylalanine for valine in the transmembrane domain of the mature protein. This mutation was present in DNA from all four examined affected individuals and linked to the disease with a lod score of 3.25, and was the most probable cause of AD in this family.

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