Mutations

APP K724N (Belgian)

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease
Genomic Mutation Name (MET1): g.275364G>C
Genomic Mutation Name (NT1): g.284060G>C
dbSNP ID: rs63750151
Coding/Non-Coding: Coding
Genomic Region: Exon 17
Mutation Type: Point, Missense
Codon Change: AAG to AAC

Findings

This mutation, which is just outside the transmembrane domain of APP, was first described in a Belgian patient who began having memory problems at the age of 55 and fulfilled the criteria of probable AD. She had a family history of dementia. Her father was diagnosed with Pick's disease at the age of 52 and died without autopsy at the age of 56. The proband's symptoms included progresive impairment of episodic memory and executive functioning. Other symptoms included anxiety, depression, and apathy (Theuns et al., 2006).

Neuropathology

The mutation carrier had significantly more amyloid across the cerebral cortex than control subjects as measured by PiB-PET (Theuns et al., 2006).

Biological Effect

A significantly increased Aβ42/Aβ40 ratio was measured in the conditioned media of K724N transfected HEK293T cells. A similar increase was measured in primary mouse neurons due to an increase in Aβ42 and a decrease in Aβ40 (Theuns et al., 2006).

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References

Paper Citations

  1. . Alzheimer dementia caused by a novel mutation located in the APP C-terminal intracytosolic fragment. Hum Mutat. 2006 Sep;27(9):888-96. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . Alzheimer dementia caused by a novel mutation located in the APP C-terminal intracytosolic fragment. Hum Mutat. 2006 Sep;27(9):888-96. PubMed.