Mutations

APP E693K (Italian)

Overview

Pathogenicity: Cerebral Amyloid Angiopathy : Pathogenic
Clinical Phenotype: Cerebral Amyloid Angiopathy
Genomic Mutation Name (MET1): g.275269G>A
Genomic Mutation Name (NT1): g.283965G>A
dbSNP ID: rs63750579
Coding/Non-Coding: Coding
Genomic Region: Exon 17
Mutation Type: Point, Missense
Codon Change: GAA to AAA

Findings

This mutation was originally identified in four Italian families who had a form of familial cerebral amyloid angiopathy (CAA). Affected individuals presented with recurrent headaches and multiple strokes followed frequently by epilepsy and cognitive decline (Tagliavini et al., 1999).

Neuropathology

Neuroimaging showed small to large hematomas, subarachnoid bleeding, scars with hemosiderin deposits, small infarcts, and leukoaraiosis. Aβ immunoreactivity was detected in the walls of leptomeningeal and parenchymal vessels and in the neuropil. This disease is distinguished from Alzheimer's disease with CAA by the absence of neurofibrillary changes and neuritic plaques (Tagliavini et al., 1999; Bugiani et al., 2010).

Biological Effect

HEK cells transfected with mutant APP produced significantly lower amounts of Aβ42, while levels of Aβ40 were similar to those produced by wild-type APP. Therefore, the ratio of Aβ42/Aβ40 was reduced (Nilsberth et al., 2001).

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References

Paper Citations

  1. . A new βPP mutation related to hereditary cerebral haemorrhage. Alzheimer's Reports 2 Supp 1: S28, 1999
  2. . Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP. Arch Neurol. 2010 Aug;67(8):987-95. PubMed.
  3. . The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat Neurosci. 2001 Sep;4(9):887-93. PubMed.

Further Reading

Learn More

Alzheimer Disease & Frontotemporal Dementia Mutation Database

Primary Papers

  1. . A new βPP mutation related to hereditary cerebral haemorrhage. Alzheimer's Reports 2 Supp 1: S28, 1999
  2. . Hereditary cerebral hemorrhage with amyloidosis associated with the E693K mutation of APP. Arch Neurol. 2010 Aug;67(8):987-95. PubMed.

Other mutations at this position

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