Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides

Topic: Brain proteins, microglia and lab models

Deposits of amyloid fibers are found in large numbers in the walls of blood vessels and in neuritic plaques in the brains of patients with Alzheimer disease and adults with Down syndrome. We used the amino acid sequence of the amyloid peptide to synthesize oligonucleotide probes specific for the gene encoding this peptide. When a human brain cDNA library was screened with this probe, a clone was found with a 1.7-kilobase insert that contains a long open reading frame coding for 412 amino acid residues including the 28 amino acids of the amyloid peptide. RNA gel blots revealed that a 3.3-kilobase mRNA species was present in the brains of individuals with Alzheimer disease, with Down syndrome, or with no apparent neurological disorders. Southern blots showed that homologous genes are present in the genomic DNA of humans, rabbits, sheep, hamsters, and mice, suggesting that this gene has been conserved through mammalian evolution. Localization of the corresponding genomic sequences on human chromosome 21 suggests a genetic relationship between Alzheimer disease and Down syndrome, and it may explain the early appearance of large numbers of neuritic plaques in adult Down syndrome patients.

Key findings

• RNA gel blots revealed that a 3.3-kilobase mRNA species was present in the brains of individuals with Alzheimer disease, with Down syndrome, or with no apparent neurological disorders.
• Southern blots showed that homologous genes are present in the genomic DNA of humans, rabbits, sheep, hamsters, and mice, suggesting that this gene has been conserved through mammalian evolution.

Why it matters

This study identified and cloned a gene encoding the amyloid peptide found in Alzheimer's brain deposits and located it on human chromosome 21. It provides a possible genetic link between Alzheimer's disease and Down syndrome but does not itself offer a treatment or cure.

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1073/pnas.84.12.4190
• PubMed: 3035574
• 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{robakis1987-3035574,
  author  = {Robakis, N. K. and Ramakrishna, N. and Wolfe, G. and Wisniewski, H. M.},
  title   = {{Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides}},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year    = {1987},
  doi     = {10.1073/pnas.84.12.4190},
  pmid    = {3035574},
  url     = {https://doi.org/10.1073/pnas.84.12.4190}
}

Studies this one cites

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

• Alzheimer's disease in Down's syndrome: clinicopathologic studies Neurology · 1985-07-01 · usefulness score 61/100 · Getting a diagnosis
• 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

Later studies that cite this one

26 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
• 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
• Probing the biology of Alzheimer's disease in mice Neuron · 2010-06-01 · usefulness score 50/100 · Getting a diagnosis
• Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein Proceedings of the National Academy of Sciences of the United States of America · 1992-04-01 · usefulness score 50/100 · Risk genes beyond APOE
• Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues Proceedings of the National Academy of Sciences of the United States of America · 1988-10-01 · usefulness score 49/100 · Risk genes beyond APOE
• Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease Acta Neuropathologica · 2025-06-03 · usefulness score 48/100 · Biomarkers
• Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation Proceedings of the National Academy of Sciences of the United States of America · 1990-08-01 · usefulness score 48/100 · Risk genes beyond APOE

Related studies in Down syndrome and Alzheimer's

• Sequence of Deposition of Heterogeneous Amyloid β-Peptides and APO E in Down Syndrome: Implications for Initial Events in Amyloid Plaque Formation Neurobiology of Disease · 1996-02-01 · usefulness score 51/100
• Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn Mammalian genome : official journal of the International Mammalian Genome Society · 2011-09-28 · usefulness score 36/100
• 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
• 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
• Alzheimer's disease and Down's syndrome: Sharing of a unique cerebrovascular amyloid fibril protein Biochemical and Biophysical Research Communications · 1984-08-01 · usefulness score 47/100
• The amyloid plaque proteome in early onset Alzheimer's disease and Down syndrome Acta neuropathologica communications · 2022-04-13 · usefulness score 43/100

Similar studies

• Molecular genetics of Alzheimer's disease and the amyloid beta peptide precursor gene 1989 · Down syndrome and Alzheimer's
• Molecular misreading of genes in Down syndrome as a model for the Alzheimer type of neurodegeneration 1999 · Down syndrome and Alzheimer's
• Preparation of a recombinant cDNA library from poly(A+) RNA of the Alzheimer brain. Identification and characterization of a cDNA copy encoding a glial-specific protein 1988 · Biomarkers
• Characterization and Chromosomal Localization of a cDNA Encoding Brain Amyloid of Alzheimer's Disease 1987 · Risk genes beyond APOE
• Reexpression of a developmentally regulated antigen in Down syndrome and Alzheimer disease 1988 · Down syndrome and Alzheimer's
• Genetic studies support a neuronal origin for the beta amyloid polypeptide 1989 · Down syndrome and Alzheimer's

More on Down syndrome and Alzheimer's

• A review that covers this ground Beyond amyloid: Immune, cerebrovascular, and metabolic contributions to Alzheimer disease in people with Down syndrome Neuron · 2022-04-25 · usefulness score 40/100
• 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 →