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

Topic: Brain proteins, microglia and lab models

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.

Key findings

• 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.

Why it matters

The study describes how the BRI2 gene binds amyloid-beta precursor protein and inhibits amyloid-beta production, but the mechanisms regulating this processing remain poorly understood. It is a laboratory finding and does not demonstrate a treatment, cure, or prevention for Alzheimer's disease.

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Study details

• Evidence strengthLow

Read the original

• DOI: 10.1074/jbc.c500217200
• PubMed: 15983050
• Original source →
• Free full text: Journal of Biological Chemistry →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{matsuda2005-15983050,
  author  = {Matsuda, S. and Giliberto, L. and Matsuda, Y. and Davies, P. and McGowan, E. and Pickford, F. and Ghiso, J. and Frangione, B. and others},
  title   = {{The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production}},
  journal = {The Journal of biological chemistry},
  year    = {2005},
  doi     = {10.1074/jbc.c500217200},
  pmid    = {15983050},
  url     = {https://doi.org/10.1074/jbc.c500217200}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease Nature · 1995-06-01 · usefulness score 64/100 · Genetics
• β-Secretase Cleavage of Alzheimer's Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE Science · 1999-10-22 · usefulness score 64/100 · Disease mechanisms
• Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease Nature · 1991-02-21 · usefulness score 63/100 · Genetics
• The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor Nature · 1987-02-01 · usefulness score 58/100 · Disease mechanisms
• Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus Science (New York, N.Y.) · 1987-02-01 · usefulness score 57/100 · Down syndrome and Alzheimer's
• A stop-codon mutation in the BRI gene associated with familial British dementia Nature · 1999-06-01 · usefulness score 52/100 · Brain tissue and pathology
• A decamer duplication in the 3' region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred Proceedings of the National Academy of Sciences of the United States of America · 2000-04-01 · usefulness score 50/100 · Brain tissue and pathology

Later studies that cite this one

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• Copper inhibits beta-amyloid production and stimulates the non-amyloidogenic pathway of amyloid-precursor-protein secretion The Biochemical journal · 1999-12-01 · usefulness score 41/100
• Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation The Journal of biological chemistry · 2004-01-06 · usefulness score 48/100
• Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production Nature · 1992-12-01 · usefulness score 58/100
• Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation Proceedings of the National Academy of Sciences of the United States of America · 1994-12-01 · usefulness score 48/100
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