Cerebral amyloid angiopathy and parenchymal amyloid deposition in transgenic mice expressing the Danish mutant form of human BRI2

Ruben Vidal, Ana G. Barbeito, Leticia Miravalle, Bernardino Ghetti

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease clinically characterized by the presence of cataracts, hearing impairment, cerebellar ataxia and dementia. Neuropathologically, FDD is characterized by the presence of widespread cerebral amyloid angiopathy (CAA), parenchymal amyloid deposition and neurofibrillary tangles. FDD is caused by a 10-nucleotide duplication-insertion in the BRI2 gene that generates a larger-than-normal precursor protein, of which the Danish amyloid subunit (ADan) comprises the last 34 amino acids. Here, we describe a transgenic mouse model for FDD (Tg-FDD) in which the mouse Prnp (prion protein) promoter drives the expression of the Danish mutant form of human BRI2. The main neuropathological findings in Tg-FDD mice are the presence of widespread CAA and parenchymal deposition of ADan. In addition, we observe the presence of amyloid-associated gliosis, an inflammatory response and deposition of oligomeric ADan. As the animals aged, they showed abnormal grooming behavior, an arched back, and walked with a wide-based gait and shorter steps. This mouse model may give insights on the pathogenesis of FDD and will prove useful for the development of therapeutics. Moreover, the study of Tg-FDD mice may offer new insights into the role of amyloid in neurodegeneration in other disorders, including Alzheimer disease.

Original languageEnglish (US)
Pages (from-to)58-68
Number of pages11
JournalBrain Pathology
Volume19
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • AD
  • Amyloid
  • CAA
  • FBD
  • FDD
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

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