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A novel APP mutation (D678H) in a Taiwanese patient exhibiting dementia and cerebral microvasculopathy

Min-Yu Lan1, Jia-Shou Liu2, Yi-Shan Wu2

  • 1Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung 833, Taiwan; Center for Parkinson's Disease, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia
|August 13, 2013
PubMed

Insights

A novel APP gene mutation (D678H) was found in a Taiwanese patient with progressive dementia. This mutation is linked to cerebral amyloid angiopathy and increased beta-amyloid peptide deposition in the brain.

Area of Science:

  • Neuroscience
  • Genetics
  • Pathology

Background:

  • The APP gene plays a critical role in amyloid precursor protein processing.
  • Mutations in the APP gene are associated with early-onset Alzheimer's disease and cerebral amyloid angiopathy.
  • Cerebral amyloid angiopathy involves beta-amyloid peptide deposition in cerebral blood vessels.

Observation:

  • A Taiwanese patient presented with progressive cognitive decline starting in middle age.
  • Brain MRI revealed leukoencephalopathy, microhemorrhages, and superficial cortical hemosiderosis.
  • These findings are indicative of cerebral amyloid angiopathy.

Findings:

  • A novel missense mutation, D678H, was identified in the APP gene of the patient.
  • The patient's phenotype suggested concurrent increases in brain parenchymal and cerebrovascular beta-amyloid peptide (Aβ) deposition.
  • The D678H mutation is postulated to promote Aβ aggregation, underlying the observed pathology.

Implications:

  • This discovery expands the known spectrum of APP mutations associated with neurodegenerative diseases.
  • Understanding the pathogenic mechanism of the D678H mutation could offer new therapeutic targets.
  • Further research is warranted to elucidate the precise role of this mutation in Aβ aggregation and cerebrovascular disease.
Keywords:
Alzheimer’s diseaseAmyloid precursor proteinBeta-amyloid peptideCerebral amyloid angiopathyMutation

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