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

36 Citations (Scopus)

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 1 2009

Fingerprint

Cerebral Amyloid Angiopathy
Amyloid
Transgenic Mice
Grooming
Cerebellar Ataxia
Neurofibrillary Tangles
Gliosis
Protein Precursors
Familial Danish dementia
Gait
Hearing Loss
Neurodegenerative Diseases
Cataract
Dementia
Alzheimer Disease
Nucleotides
Amino Acids

Keywords

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

ASJC Scopus subject areas

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

Cite this

Cerebral amyloid angiopathy and parenchymal amyloid deposition in transgenic mice expressing the Danish mutant form of human BRI2. / Vidal, Ruben; Barbeito, Ana G.; Miravalle, Leticia; Ghetti, Bernardino.

In: Brain Pathology, Vol. 19, No. 1, 01.01.2009, p. 58-68.

Research output: Contribution to journalArticle

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