Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21

Topic: Brain proteins, microglia and lab models

The gene encoding the beta-amyloid precursor protein has been assigned to human chromosome 21, as has a gene responsible for at least some cases of familial Alzheimer disease. Linkage studies strongly suggest that the beta-amyloid precursor protein and the product corresponding to familial Alzheimer disease are from two genes, or at least that several million base pairs of DNA separate the markers. The precise location of the beta-amyloid precursor protein gene on chromosome 21 has not yet been determined. Here we show, by using a somatic-cell/hybrid-cell mapping panel, in situ hybridization, and transverse-alternating-field electrophoresis, that the beta-amyloid precursor protein gene is located on chromosome 21 very near the 21q21/21q22 border and probably within the region of chromosome 21 that, when trisomic, results in Down syndrome.

Key findings

• Linkage studies strongly suggest that the beta-amyloid precursor protein and the product corresponding to familial Alzheimer disease are from two genes, or at least that several million base pairs of DNA separate the markers.
• Here we show, by using a somatic-cell/hybrid-cell mapping panel, in situ hybridization, and transverse-alternating-field electrophoresis, that the beta-amyloid precursor protein gene is located on chromosome 21 very near the 21q21/21q22 border and probably within the region of chromosome 21 that, when trisomic, results in Down syndrome.

Why it matters

This mapping study located the beta-amyloid precursor protein gene on chromosome 21 near the region that causes Down syndrome when trisomic. It is basic genetics and provides no treatment, cure or prevention for Alzheimer's disease.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1073/pnas.85.21.8266
• PubMed: 2973063
• Original source →
• Free full text: PubMed Central →

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

@article{patterson1988-2973063,
  author  = {Patterson, D. and Gardiner, K. and Kao, F. T. and Tanzi, R. and Watkins, P. and Gusella, J. F.},
  title   = {{Mapping of the gene encoding the beta-amyloid precursor protein and its relationship to the Down syndrome region of chromosome 21}},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year    = {1988},
  doi     = {10.1073/pnas.85.21.8266},
  pmid    = {2973063},
  url     = {https://doi.org/10.1073/pnas.85.21.8266}
}

Studies this one cites

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

• 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
• 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
• Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides Proceedings of the National Academy of Sciences of the United States of America · 1987-06-01 · usefulness score 45/100 · Down syndrome and Alzheimer's

Later studies that cite this one

3 studies in the alzhub library list this one in their references.

• The Alzheimer amyloid precursor protein maps to human chromosome 21 bands q21.105-q21.05 Genomics · 1989-07-01 · usefulness score 39/100 · Down syndrome and Alzheimer's
• High expression on Kunitz-type protease inhibitor-containing substances in the cerebral vessels of patients with Down syndrome The Tohoku journal of experimental medicine · 1994-11-01 · usefulness score 28/100 · Down syndrome and Alzheimer's
• Cerebrovascular disease drives Alzheimer plasma biomarker concentrations in adults with Down syndrome medRxiv · 2023-11-29 · usefulness score 16/100 · Down syndrome and Alzheimer's

Related studies in Down syndrome and Alzheimer's

• The promoter activity of the gene encoding Alzheimer beta-amyloid precursor protein (APP) is regulated by two blocks of upstream sequences Brain research. Molecular brain research · 1991-02-01 · usefulness score 37/100
• A nuclear factor-binding domain in the 5'-untranslated region of the amyloid precursor protein promoter: implications for the regulation of gene expression BMC research notes · 2010-01-12 · usefulness score 31/100
• 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
• Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch) Science (New York, N.Y.) · 1990-06-01 · usefulness score 41/100
• Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome Neuroscience letters · 2002-06-01 · usefulness score 38/100
• Molecular genetics of Alzheimer's disease and the amyloid beta peptide precursor gene Annals of medicine · 1989-01-01 · usefulness score 36/100

Also tagged “down”

527 studies in the library carry the topic tag “down”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 527 tagged studies.

• Down syndrome Current opinion in neurology · 1997-04-01 · usefulness score 31/100 · Down syndrome and Alzheimer's
• Detection of an Alzheimer disease pattern of cerebral metabolism in Down syndrome Dementia (Basel, Switzerland) · 1994-03-01 · usefulness score 50/100 · Down syndrome and Alzheimer's
• Fecal corticosterone levels in RCAN1 mutant mice Comparative medicine · 2012-04-01 · usefulness score 30/100 · Down syndrome and Alzheimer's

Similar studies

• Beta-amyloid protein probe hybridized to chromosome 9 in 3 Alzheimer disease individuals 1989 · Down syndrome and Alzheimer's
• Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17 1988 · Down syndrome and Alzheimer's
• Expression of the amyloid precursor protein gene in mouse oocytes and embryos 1991 · Down syndrome and Alzheimer's
• Influence of the amyloid precursor protein locus on dementia in Down syndrome 2004 · Down syndrome and Alzheimer's
• Age-associated chromosome 21 loss in Down syndrome: possible relevance to mosaicism and Alzheimer disease 1993 · Down syndrome and Alzheimer's
• Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome 2003 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground beta-Amyloid precursor protein metabolites and loss of neuronal Ca2+ homeostasis in Alzheimer's disease Trends in neurosciences · 1993-10-01 · 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 →