Mutations

APP M722K

Overview

Pathogenicity: Alzheimer's Disease : Pathogenic
Clinical Phenotype: Alzheimer's Disease, None
Reference Assembly: GRCh37 (105)
Position: Chr21:27264080 T>A
dbSNP ID: NA
Coding/Non-Coding: Coding
Mutation Type: Point, Missense
Codon Change: ATG to AAG
Reference Isoform: APP Isoform APP770 (770 aa)
Genomic Region: Exon 17

Findings

This mutation in APP was reported in a Chinese family affected by early onset Alzheimer’s disease (Wang et al., 2015). The proband developed memory problems at the age of 38 and met NINCDS-ADRDA criteria for AD by age 42. The reported pedigree shows four additional affected family members over three generations. Symptoms were typical for AD, e.g., decline in memory and executive functioning, as well as depression. There was a strong family history, but the mutation could not be shown conclusively to segregate with disease. It was absent in an unaffected sibling (age 58), but present in another unaffected sibling (age 42). The authors speculate that the unaffected mutation carrier may be presymptomatic.

Neuropathology

Unknown. MRI of the proband at age 42 showed moderate cerebral atrophy, especially in the hippocampus.

Biological Effect

N2a neuroblastoma cells expressing APP (isoform 695) with the M722K mutation had elevated levels of Aβ42 in conditioned media and cell lysates compared with cells expressing wild-type APP. Differences in Aβ40 were not significant. There was a 1.7-fold increase in the Aβ42/Aβ40 ratio compared to cells expressing wild-type APP. In addition, cells expressing the mutant APP also had more phospho-tau as detected by the AT8 antibody.

Last Updated: 13 May 2016

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References

Paper Citations

  1. . A Novel AβPP M722K Mutation Affects Amyloid-β Secretion and Tau Phosphorylation and May Cause Early-Onset Familial Alzheimer's Disease in Chinese Individuals. J Alzheimers Dis. 2015;47(1):157-65. PubMed.

Further Reading

No Available Further Reading

Protein Diagram

Primary Papers

  1. . A Novel AβPP M722K Mutation Affects Amyloid-β Secretion and Tau Phosphorylation and May Cause Early-Onset Familial Alzheimer's Disease in Chinese Individuals. J Alzheimers Dis. 2015;47(1):157-65. PubMed.

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