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Cited by 60Alzheimer's disease research and treatmentsIntracerebral and Subarachnoid Hemorrhage ResearchNeuroinflammation and Neurodegeneration Mechanisms

Cerebral Amyloid Angiopathy and Parenchymal Amyloid Deposition in Transgenic Mice Expressing the Danish Mutant Form of Human BRI2

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Vidal, Ruben, Barbeito, Ana G., Miravalle, Leticia, Ghetti, Bernardino·2009·Brain Pathology
DOI 10.1111/j.1750-3639.2008.00164.xPMC PMC2605177
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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 BRI 2 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 BRI 2 . 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.

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  • The Tg-FDD mouse model accumulates Danish amyloid exclusively in the vasculature.

    “The Tg-FDD mouse model accumulates Danish amyloid exclusively in the vasculature.”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [88]

    The Discussion (page not provided) reports parenchymal ADan deposition, including some amyloid deposits in the cortex and hippocampus. The model therefore does not accumulate Danish amyloid exclusively in the vasculature. (LLM, conf=0.95)

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Authors
Vidal, R., Barbeito, A. G., Miravalle, L., & Ghetti, B.
Affiliations
Indiana University Indianapolis (US)
ORCID
Ghetti, Bernardino
Venue
Brain Pathology
Publisher
Wiley
Published
2008-12-03
Volume
19
Issue
1
Pages
58-68
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/j.1750-3639.2008.00164.x
PMC
PMC2605177
OpenAlex
W2051562436
Cited by
60
References
3
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 8 · 2014: 4 · 2013: 2 · 2012: 3
FWCI
3.61
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Brain Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Chinese Academy of Agricultural Sciences
  • National Institute on Aging (AG 10133, P30AG010133)
  • National Institute of Neurological Disorders and Stroke (R01NS050227, NS050227)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
familial Danish dementia, cerebral amyloid angiopathy, BRI2, transgenic mouse model, neuroinflammation, oligomeric amyloid, neurodegeneration, Alzheimer's disease
MeSH terms
Prion Proteins, Age Factors, Animals, Brain, Dementia, Denmark, Disease Models, Animal, Grooming, Humans, Immunohistochemistry, Membrane Glycoproteins, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Prions, Blotting, Western, Gene Expression, Polymerase Chain Reaction, Walking, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Adaptor Proteins, Signal Transducing, Mice

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