Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice

Nature Medicine

Volumn 3, Issue 1, 1997, Pages 67-72

  Citron, Martin ^a   Westaway, David ^b   Xia, Weiming ^a   Carlson, George ^c   Diehl, Thekla ^a   Levesque, Georges ^b   Johnson Wood, Kelly ^d   Lee, Michael ^d   Seubert, Peter ^d   Davis, Angela ^c   Kholodenko, Dora ^d   Motter, Ruth ^d   Sherrington, Robin ^b   Perry, Billie ^c   Yao, Hong ^b   Strome, Robert ^b   Lieberburg, Ivan ^d   Rommens, Johanna ^b   Kim, Soyeon ^e   Schenk, Dale ^d   Fraser, Paul ^b   St George Hyslop, Peter ^b   Selkoe, Dennis J ^a   more..

^a HARVARD MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF TORONTO   (Canada)

^c McLauglin Research Institute   (United States)

^d Athena Neurosciences Inc   (United States)

^e HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; PRESENILIN 1; PRESENILIN 2;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; GENE EXPRESSION; MOUSE; MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS; TRANSGENIC MOUSE;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BRAIN; CELL LINE; ENZYME-LINKED IMMUNOSORBENT ASSAY; GENETIC VECTORS; HIPPOCAMPUS; HUMANS; MEMBRANE PROTEINS; MICE; MICE, TRANSGENIC; MUTATION; PEPTIDE FRAGMENTS; PRESENILIN-1; PRESENILIN-2; TRANSFECTION;

EID: 16944362157     PISSN: 10788956     EISSN: None     Source Type: Journal    
DOI: 10.1038/nm0197-67     Document Type: Article

References (28)

1. Selkoe, D.J. Amyloid β-protein and the genetics of Alzheimer's disease. J. Biol. Chem. 271, 18295-18296 (1996).
2. Jarrett, J.T., Berger, E.P. & Lansbury P.T., Jr. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease. Biochemistry 32, 4693-4697 (1993).
3. Scheuner, D. et al. Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nature Med. 2, 864-870 (1996).
4. Yankner, B.A. New clues to Alzheimer's disease: Unraveling the roles of amyloid and tau. Nature Med. 2, 850-852 (1996).
5. Citron, M. et al. Inhibition of amyloid β-protein production in neural cells by the serine protease inhibitor AEBSF. Neuron 17, 171-179 (1996).
6. Citron, M., Teplow, D.B. & Selkoe, D.J. Generation of amyloid β-protein from its precursor is sequence specific. Neuron 14, 661-670 (1995).
7. Knops, J. et al. Cell-type and amyloid precursor protein-type specific inhibition of Aβ release by Bafilomycin A1, a selective inhibitor of vacuolar ATPases. J. Biol. Chem. 270, 2419-2422 (1995).
8. Haass, C. et al. The Swedish mutation causes early-onset alzheimer's disease by β-secretase cleavage within the secretory pathway. Nature Med. 1, 1291-1296 (1995).
9. Thinakaran, G. et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190 (1996).
10. Walter, J. et al. The Alzheimer's disease associated presenilins are differentially phosphorylated proteins located predominantly within the endoplasmic reticulum. Mol. Med. (in the press).
11. Podlisny, MB., Tolan, D. & Selkoe, D.J. Homology of the amyloid β-protein precursor in monkey and human supports a primate model for β-amyloidosis in Alzheimer's disease. Am. J. Pathol. 138, 1423-1435(1991).
12. Haass, C., Hung, A.Y., Selkoe, D.J. & Teplow, D.B. Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid β-protein precursor. J. Biol. Chem. 269, 17741-17748 (1994).
13. Haass, C. et al. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 359, 322-325 (1992).
14. Citron, M. et al. Evidence that Aβ42 and Aβ40 are generated from the β-amyloid precursor protein by different protease activities. Proc. Natl. Acad. Sci. USA 93, 13170-13175 (1996).
15. Scott, M.R., Kohler, R., Foster, D. & Prusiner, S.B. Chimeric prion protein expression in cultured cells and transgenic mice. Protein Sci. 1, 986-997 (1992).
16. Prusiner, S., Scott, M., Foster, D., Westaway, D. & DeArmond, S. Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63, 673-686 (1990).
17. Moser, M., Colello, R.J., Pott, U. & Oesch, B. Developmental expression of the PrP gene in glial cells. Neuron 14, 509-517 (1995).
18. Hsiao, K.K. et al. Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron 15, 1203-1218 (1995).
19. Sherrington, R. et al. Cloning of a novel gene bearing missense mutations in early onset familial Alzheimer disease. Nature 375, 754-760 (1995).
20. Rogaev, E.I. et al. Analysis of the 5′ sequence, genomic structure and alternative splicing of the presenilin 1 gene associated with early onset alzheimer's disease. Genomics (in the press).
21. Foncin, J.F. et al. Alzheimer's presenile dementia transmitted in an extended kindred. Rev. Neurol. (Paris) 141, 194-202 (1985).
22. Frommelt, P., Schnabel, R., Kuhne, W., Nee, L.E. & Polinsky, R.J. Familial Alzheimer disease: A large multigenerational German kindred. Alzheimer Dis. Assoc. Disorders 5, 36-43 (1991).
23. Seubert, P. et al. Secretion of β-amyloid precursor protein cleaved at the amino-terminus of the β-amyloid peptide. Nature 361, 260-263 (1993).
24. Radzicka, A. & Wolfenden, R. Comparing the polarities of the amino acids: Side-chain distribution coefficients between the vapor phase, cyclohexane, 1-octanol, and neutral aqueous solution. Biochemistry 27, 1664-1670 (1988).
25. Sherrington, R. et al. Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant. Hum. Mol. Genetics 5, 985-988 (1996).
26. Lemere, C.A. et al. The E280A presenilin 1 Alzheimer mutation produces increased Aβ42 deposition and severe cerebellar pathology. Nature Med. 2, 1146-1150 (1996).
27. Rogaev, E.I. et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775-778 (1995).
28. Seubert, P. et al. Isolation and quantitation of soluble Alzheimer's β-peptide from biological fluids. Nature 359, 325-327 (1992).