Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus

Topic: Amyloid, tau and blood-test diagnosis

The amyloid beta protein has been identified as an important component of both cerebrovascular amyloid and amyloid plaques of Alzheimer's disease and Down syndrome. A complementary DNA for the beta protein suggests that it derives from a larger protein expressed in a variety of tissues. Overexpression of the gene in brain tissue from fetuses with Down syndrome (trisomy 21) can be explained by dosage since the locus encoding the beta protein maps to chromosome 21. Regional localization of this gene by both physical and genetic mapping places it in the vicinity of the genetic defect causing the inherited form of Alzheimer's disease.

@article{tanzi1987-2949367,
  author  = {Tanzi, R. E. and Gusella, J. F. and Watkins, P. C. and Bruns, G. A. and St George-Hyslop, P. and Van Keuren, M. L. and Patterson, D. and Pagan, S. and others},
  title   = {{Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus}},
  journal = {Science (New York, N.Y.)},
  year    = {1987},
  doi     = {10.1126/science.2949367},
  pmid    = {2949367},
  url     = {https://doi.org/10.1126/science.2949367}
}

Key findings

• A complementary DNA for the beta protein suggests that it derives from a larger protein expressed in a variety of tissues.

Why it matters

This 1987 lab study isolated a DNA copy of the gene for amyloid beta, a main component of the plaques and blood-vessel amyloid seen in Alzheimer's disease and Down syndrome. The authors report that this suggests the protein comes from a larger protein made in many tissues, and that the gene sits on chromosome 21, which could explain why it was over-expressed in brain tissue from fetuses with Down syndrome (who carry an extra copy of that chromosome). Mapping placed the gene near the genetic defect behind inherited Alzheimer's (near, not shown to be that defect), and the study tested no treatment or prevention.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1126/science.2949367
• PubMed: 2949367
• Original source →

May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.

Studies this one cites

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

• Amyloid plaque core protein in Alzheimer disease and Down syndrome Proceedings of the National Academy of Sciences of the United States of America · 1985-06-01 · usefulness score 56/100 · Down syndrome and Alzheimer's
• Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein Biochemical and Biophysical Research Communications · 1984-05-01 · usefulness score 54/100 · Disease mechanisms
• Senile dementia of the Alzheimer type Annals of neurology · 1983-11-01 · usefulness score 48/100 · Getting a diagnosis

Later studies that cite this one

78 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.

• The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics Science · 2002-07-19 · usefulness score 65/100 · Disease mechanisms
• Mild cognitive impairment Lancet (London, England) · 2006-04-01 · usefulness score 64/100 · Prevention and risk
• 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
• Alzheimer's Disease: The Amyloid Cascade Hypothesis Science · 1992-04-10 · usefulness score 61/100 · Disease mechanisms
• Alzheimer's disease: the challenge of the second century Science translational medicine · 2011-04-01 · usefulness score 57/100 · How common it is
• Interactions of pathological proteins in neurodegenerative diseases Acta neuropathologica · 2017-04-11 · usefulness score 56/100 · Lewy body dementia
• A mouse model for Down syndrome exhibits learning and behaviour deficits Nature genetics · 1995-10-01 · usefulness score 54/100 · Down syndrome and Alzheimer's
• Not just amyloid: physiological functions of the amyloid precursor protein family Nature reviews. Neuroscience · 2017-03-31 · usefulness score 53/100 · Risk genes beyond APOE

Related studies in Down syndrome and Alzheimer's

• The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene Nature · 1987-09-01 · usefulness score 41/100
• Nerve growth factor increases mRNA levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain Proceedings of the National Academy of Sciences of the United States of America · 1988-12-01 · usefulness score 43/100
• Chronic elevation of S100 beta protein does not alter APP mRNA expression or promote beta-amyloid deposition in the brains of aging transgenic mice Brain research · 1995-12-01 · usefulness score 33/100
• Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21 Proceedings of the National Academy of Sciences of the United States of America · 1988-11-01 · usefulness score 44/100
• Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch) Science (New York, N.Y.) · 1990-06-01 · usefulness score 41/100
• The mouse homolog of the human amyloid beta protein (AD-AP) gene is located on the distal end of mouse chromosome 16: further extension of the homology between human chromosome 21 and mouse chromosome 16 Biochemical and biophysical research communications · 1987-04-01 · usefulness score 40/100

Also tagged “precursor”

1,339 studies in the library carry the topic tag “precursor”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,339 tagged studies.

• Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease Neurobiology of disease · 2008-01-05 · usefulness score 46/100 · Mild cognitive impairment
• Cerebral small vessel disease-induced apolipoprotein E leakage is associated with Alzheimer disease and the accumulation of amyloid beta-protein in perivascular astrocytes Journal of neuropathology and experimental neurology · 2008-09-01 · usefulness score 39/100 · Genetics
• The Link between Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation in the Pathophysiology of Alzheimer's Disease: Therapeutic Implications and Future Perspectives Antioxidants (Basel, Switzerland) · 2022-10-31 · usefulness score 45/100 · Caregiving

Similar studies

• Characterization and Chromosomal Localization of a cDNA Encoding Brain Amyloid of Alzheimer's Disease 1987 · Risk genes beyond APOE
• Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome 2015 · Biomarkers
• Genetic studies support a neuronal origin for the beta amyloid polypeptide 1989 · Down syndrome and Alzheimer's
• Beta-amyloid protein probe hybridized to chromosome 9 in 3 Alzheimer disease individuals 1989 · Down syndrome and Alzheimer's
• Candidate Gene for the Chromosome 1 Familial Alzheimer's Disease Locus 1995 · Risk genes beyond APOE
• The Genetics and Mechanisms of Alzheimer's Disease in Down Syndrome 2026 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground Molecular genetics of Alzheimer's disease and the amyloid beta peptide precursor gene Annals of medicine · 1989-01-01 · usefulness score 36/100
• Newest in this subject Differential endothelial cell remodeling in Down syndrome and APP duplication drives distinct blood brain barrier dysfunction bioRxiv · 2026-10-30 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Memory and Plasma pTau217 Refine Prognosis in Down Syndrome Annals of neurology · 2026-10-02 · Peer-reviewed · usefulness score 47/100

See all studies in Down syndrome and Alzheimer's →