Increased β‐amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the Swedish Alzheimer's disease APP670/671 mutation

@article{Johnston1994IncreasedR,
  title={Increased $\beta$‐amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the Swedish Alzheimer's disease APP670/671 mutation},
  author={Janet A. Johnston and Richard F. Cowburn and Svante Norgren and Birgitta Wiehager and Nikolaos Venizelos and Bengt Winblad and Carmen Vigo‐Pelfrey and Dale B. Schenk and Lars Lannfelt and Cora O'Neill},
  journal={FEBS Letters},
  year={1994},
  volume={354}
}
Cell lines transfected with the Swedish Alzheimer's disease amyloid precursor protein APP670/671 mutation release significantly more β‐amyloid than wild‐type cells. Citron et al. [Proc. Natl. Acad. Sci. USA (1994) in press] have recently shown that fibroblasts carrying the APP670/671 mutation also release more β‐amyloid than control cells [1]. The present study confirms a ca. threefold increase in β‐amyloid release from mutation‐bearing fibroblasts. APP mRNA levels did not differ between… Expand
Protein kinase C and amyloid precursor protein processing in skin fibroblasts from sporadic and familial Alzheimer's disease cases.
TLDR
Results indicate that PKC deficits are unlikely to contribute to increased Abeta seen with APP and PS1 mutations, and also thatPS1 mutations decrease alpha-secretase derived APPs production independently of altered PKC activity. Expand
Abnormalities in Alzheimer’s Disease Fibroblasts Bearing the APP670/671 Mutation
TLDR
Comparison of signal transduction in cell lines from multiple, genetically characterized AD families will allow testing of the hypothesis that these various pathogenic FAD abnormalities that lead to AD converge at the level of abnormal signalTransduction. Expand
The Uppsala APP deletion causes early onset autosomal dominant Alzheimer’s disease by altering APP processing and increasing amyloid β fibril formation
TLDR
The Uppsala APP deletion is described, the first reported deletion causing autosomal dominant AD, and in vitro aggregation studies and analyses of patient brain tissue samples indicate that the longer form of mutated Aβ, AβUpp1–42Δ19–24, accelerates the formation of fibrils with unique polymorphs and their deposition into amyloid plaques in the affected brain. Expand
Differential Effects of the Swedish Mutant Amyloid Precursor Protein on β-Amyloid Accumulation and Secretion in Neurons and Nonneuronal Cells*
TLDR
Results show that the Swedish ΔNL mutation causes nonneuronal cells to process APP via pathways more in common with the metabolism of wild-type APP in neurons. Expand
Flemish and Dutch Mutations in Amyloid β Precursor Protein Have Different Effects on Amyloid β Secretion
TLDR
Evidence is provided that APP692 and APP693 have a different effect on A beta secretion as determined by cDNA transfection experiments, which corroborate with previous findings that increased A Beta secretion and particularly of A beta 42, is specific for AD pathology. Expand
Unusual phenotypic alteration of β amyloid precursor protein (βAPP) maturation by a new Val-715 → Met βAPP-770 mutation responsible for probable early-onset Alzheimer’s disease
TLDR
The results suggest that, in some cases, familial AD may be associated with a reduction in the overall production of Aβ but may be caused by increased production of truncated forms of A β ending at the 42 position. Expand
Opposite changes in APP processing and human Aβ levels in rats carrying either a protective or a pathogenic APP mutation
TLDR
The Icelandic APP mutation near the BACE1-cleavage site protects from sporadic dementia, emphasizing APP’s role in dementia pathogenesis and suggesting that protection from and pathogenesis of dementia depend upon combinatorial and opposite alterations in APP metabolism rather than simply on Aβ levels. Expand
Microtubule-associated protein tau in human fibroblasts with the Swedish Alzheimer mutation
TLDR
It is concluded that increased levels of Abeta do not seem to increase the levels of tau in human fibroblasts, and it is suggested that several of the traditional tau isoforms as well as isoforms of higher molecular weights, big tau, are expressed in this cell type. Expand
The Role of the Amyloid Protein Precursor (APP) in Alzheimer's Disease: Does the Normal Function of APP Explain the Topography of Neurodegeneration?
  • D. Small
  • Biology, Medicine
  • Neurochemical Research
  • 2004
TLDR
A model of how APP and Aβ are involved in pathogenesis is presented and it is suggested that those neurons which more readily undergo neuritic sprouting and synaptic remodelling are more vulnerable to Aβ neurotoxicity. Expand
Facilitation of glutamate, but not GABA, release in Familial Alzheimer's APP mutant Knock‐in rats with increased β‐cleavage of APP
TLDR
The data support the notion that APP tunes glutamate release, and that BACE1 cleavage of the ISVAID segment of APP facilitates this function, and suggest that alterations of Bace1 processing of APP in glutamatergic synaptic vesicles could contribute to dementia. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 31 REFERENCES
Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production
TLDR
C cultured cells which express a β-APP complementary DNA bearing a double mutation found in a Swedish FAD family produce ∼6–8-fold more Aβ than cells expressing normalβ-APP, and this increase is confirmed for elucidating the fundamental mechanism of Alzheimer's disease. Expand
An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants.
TLDR
Human neuroblastoma cells transfected with constructs expressing wild-type beta APP or the beta APP717 mutants linked to familial Alzheimer's disease were compared and it was demonstrated that the 4-kilodalton A beta released from wild- type beta APP is primarily but not exclusively A beta 1-40. Expand
A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N–terminus of β–amyloid
TLDR
A double mutation at codons 670 and 671 (APP 770 transcript) in exon 16 which co–segregates with the disease in two large (probably related) early–onset Alzheimer's disease families from Sweden is identified. Expand
Increased gene expression of Alzheimer disease beta-amyloid precursor protein in senescent cultured fibroblasts.
TLDR
Regulated expression of beta-amyloid precursor protein may be an important determinant of growth and metabolic responses to serum and growth factors under physiological as well as pathological conditions. Expand
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. Expand
Release of excess amyloid beta protein from a mutant amyloid beta protein precursor.
TLDR
Human neuroblastoma cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared and this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta. Expand
Production of the Alzheimer amyloid beta protein by normal proteolytic processing.
TLDR
Human mononuclear leukemic cells expressing a beta AP-bearing, carboxyl-terminal beta APP derivative released significant amounts of a soluble 4-kilodalton beta AP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Expand
Homology of the amyloid beta protein precursor in monkey and human supports a primate model for beta amyloidosis in Alzheimer's disease.
TLDR
The authors' findings demonstrate that cynomolgus monkey and perhaps other primates provide a close animal model for examining the early transcriptional and post-translational processing of beta APP that precedes A beta P deposition during aging and in Alzheimer's disease. Expand
Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity
TLDR
It is suggested that protease inhibition by the longer APP(s) could be related to aberrant APP catabolism, and a cDNA library of a human glioblastoma cell line is isolated, together with a new cDNA which contains a 225-nucleotide insert. Expand
Amyloid β-peptide is produced by cultured cells during normal metabolism
TLDR
The unexpected identification of the 4K (Mr 4,000) Aβ and a truncated form of Aβ in media from cultures of primary cells and untransfected and β-APP-transfected cell lines grown under normal conditions provide the basis for using simple cell culture systems to identify drugs that block the formation or release of A β, the primary protein constituent of the senile plaques of Alzheimer's disease. Expand
...
1
2
3
4
...