Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease

@article{Tanzi1988ProteaseID,
  title={Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease},
  author={Rudolph E. Tanzi and Andrea I. McClatchey and Edward D. Lamperti and L Villa-komaroff and James F. Gusella and Rachael L. Neve},
  journal={Nature},
  year={1988},
  volume={331},
  pages={528-530}
}
Amyloid B-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21)1–4 and may be involved in the pathogenesis of Alzheimer's disease5. Recent molecular genetic studies have indicated that amyloid protein is encoded as part of a larger protein by a gene on human chromosome 21 (refs 6–9). The amyloid protein precursor (APP) gene is expressed in brain and in several… 
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928 Citations

A Serine Protease Inhibitor Domain Encoded Within the Alzheimer Disease-Associated Amyloid ß-Protein Precursor Gene
A crucial event in the pathogenesis of AD involves the aggregation of a 4.2 kiloDalton (kd) hydrophobic peptide referred to as the amyloid s- protein (ABP) into insoluble extracellular proteinaceous…
The Alzheimer amyloid precursor-related transcript lacking the β/A4 sequence is specifically increased in Alzheimer's disease brain
Amyloid β-protein deposition in tissues other than brain in Alzheimer's disease
TLDR
The detection of amyloid β-protein deposits in non-neural tissues and blood vessels of Alzheimer's disease patients, including skin, subcutaneous tissue and intestine is reported, indicating that a principal feature of the disease process is expressed subclinically in tissues other than brain.
Amyloid precursor protein mRNA levels in Alzheimer's disease brain.
Molecular cloning of the cDNA for a human amyloid precursor protein homolog: evidence for a multigene family.
TLDR
Northern analysis indicates that it occurs in at least two molecular forms and is transcribed in human brain, heart, lung, liver, and kidney, in addition to placenta, and APPH is the nearest relative of APP yet identified in an emerging multigene family.
Identification of different β amyloid cDNAs cloned from the brain of a patient with sporadic alzheimer's disease
A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor
TLDR
It is demonstrated that APP contains a proteinase inhibitor domain for the matrix metalloproteinase gelatinase A, which is located in the C-terminal glycosylated region of the secretory forms of APP, and that the gelatinase has an APP secretase-like activity, which hydrolyses the Lys l6-Leu l7 bond in the β-AP sequence.
Protease Nexin 1 Immunoreactivity in Senile Plaques in Alzheimer Disease and Aged Brain
TLDR
This work has shown that another completely unrelated protease inhibitor, al-antichymotrypsin, was demonstrated to be closely associated with amyloid fibrils, and this fact supports the possibility that the imbalance between protease and protease inhibitors brings about the anomalous degradation of the APP.
β-amyloid precursor detected in human cerebral cortex
Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide
TLDR
Evidence is reported that a substantial portion of the APP secreted by human mixed brain cell cultures, as well as that present in cerebrospinal fluid, is of a novel form cleaved precisely at the amino terminus of Aβ, suggesting that a secretory pathway is involved in Aβ genesis.
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References

SHOWING 1-10 OF 27 REFERENCES
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
TLDR
An apparently full-length complementary DNA clone coding for the A4 polypeptide is isolated and sequenced and suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid β-protein gene
TLDR
The detection of several recombination events with FAD suggests that the AP gene is not the site of the inherited defect underlying this disorder, and the pattern of segregation of theAP gene in FAD pedigrees is determined using restriction fragment length polymorphisms.
Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.
TLDR
The amyloid of Alzheimer's disease is similar in subunit size, composition but not sequence to the scrapie‐associated fibril and its constituent polypeptides, and the sequence and composition of NFT are not homologous to those of any of the known components of normal neurofilaments.
Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides.
TLDR
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.
Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus.
TLDR
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.
Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease.
TLDR
Four clones were isolated from an adult human brain complementary DNA library with an oligonucleotide probe corresponding to the first 20 amino acids of the beta peptide of brain amyloid from Alzheimer's disease, and the 3.5-kilobase messenger RNA was detected in mammalian brains and human thymus.
Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein.
Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C).
TLDR
The data on the structure of a gamma-trace variant protein suggests that its gene expresses a polyprotein precursor in which active peptides are flanked by basic amino acid residues that permit cleavage to liberate small internal peptides.
The mRNA for a proteinase inhibitor related to the HI-30 domain of inter-α-trypsin inhibitor also encodes α-1-microgiobulin (protein HC
TLDR
A cDNA clone from a human liver library which codes for HI-30 is isolated, and its DNA sequence is determined, which not only codes forHI-30 but also another serum protein, alpha-1-microglobulin, which has not been previously associated with ITI or HI- 30.
Elastase inhibition by the inter-alpha-trypsin inhibitor and derived inhibitors of man and cattle.
TLDR
The inhibitory properties of HI-14 and BI-14, the active 14-kDa parts released from the corresponding human and bovine inter-alpha-trypsin inhibitors, are compared and the human inhibitor shows a much lower affinity from this enzyme.
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