Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production.

Shuji Matsuda; Luca Giliberto; Yukiko Matsuda; Peter Davies; Eileen McGowan; Fiona Pickford; Jorge Ghiso; Blas Frangione; Luciano D'Adamio (Profiled Authors: Frangione, Blas; Davies, Peter)

Albert Einstein College of Medicine, Bronx, NY 10461, USA.
The Journal of biological chemistry 2005;280(32):28912-6.

Alzheimer disease (AD), the most common senile dementia, is characterized by amyloid plaques, vascular amyloid, neurofibrillary tangles, and progressive neurodegeneration. Amyloid is mainly composed by amyloid-beta (A(beta)) peptides, which are derive from processing of the beta-amyloid precursor protein (APP), better named amyloid-beta precursor protein (A(beta)PP), by secretases. The A(beta)PP intracellular domain (AID), which is released together with A(beta), has signaling function, since it modulates apoptosis and transcription. Despite its biological and pathological importance, the mechanisms regulating A(beta)PP processing are poorly understood. As cleavage of other gamma-secretase substrates is regulated by membrane bound proteins, we have postulated the existence of integral membrane proteins that bind A(beta)PP and regulate its processing. Here, we show that BRI2, a type II membrane protein, interacts with A(beta)PP. Interestingly, 17 amino acids corresponding to the NH2-terminal portion of A(beta) are necessary for this interaction. Moreover, BRI2 expression regulates A(beta)PP processing resulting in reduced A(beta) and AID levels. Altogether, these findings characterize the BRI2-A(beta)PP interaction as a regulatory mechanism of A(beta)PP processing that inhibits A(beta) production. Notably, BRI2 mutations cause familial British (FBD) and Danish dementias (FDD) that are clinically and pathologically similar to AD. Finding that BRI2 pathogenic mutations alter the regulatory function of BRI2 on A(beta)PP processing would define dysregulation of A(beta)PP cleavage as a pathogenic mechanism common to AD, FDD, and FBD.

3 Originating Grant

• 1.

  Frangione, Blas

  AMYLOID ANGIOPATHY, EARLY PLAQUES & AGING

  1 January 1990 - 31 August 2006

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 4,063,685

• 2.

  FRANGIONE, BLAS

  AMYLOIDOSIS AND ALZHEIMERS DISEASE

  1 July 1985 - 30 June 1997

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 3,049,140

• 3.

  Frangione, Blas

  Amyloidosis and Alzheimer's Disease

  1 July 1985 - 30 June 2007

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 4,467,436

Scientific Context

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