PMID- 10097173
OWN - NLM
STAT- MEDLINE
DCOM- 19990512
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 7
DP  - 1999 Mar 30
TI  - Unusual phenotypic alteration of beta amyloid precursor protein (betaAPP)
      maturation by a new Val-715 --> Met betaAPP-770 mutation responsible for probable
      early-onset Alzheimer's disease.
PG  - 4119-24
AB  - We have identified a novel beta amyloid precursor protein (betaAPP) mutation
      (V715M-betaAPP770) that cosegregates with early-onset Alzheimer's disease (AD) in
      a pedigree. Unlike other familial AD-linked betaAPP mutations reported to date,
      overexpression of V715M-betaAPP in human HEK293 cells and murine neurons reduces 
      total Abeta production and increases the recovery of the physiologically secreted
      product, APPalpha. V715M-betaAPP significantly reduces Abeta40 secretion without 
      affecting Abeta42 production in HEK293 cells. However, a marked increase in
      N-terminally truncated Abeta ending at position 42 (x-42Abeta) is observed,
      whereas its counterpart x-40Abeta is not affected. These results suggest that, in
      some cases, familial AD may be associated with a reduction in the overall
      production of Abeta but may be caused by increased production of truncated forms 
      of Abeta ending at the 42 position.
FAU - Ancolio, K
AU  - Ancolio K
AD  - Institut de Pharmacologie Moleculaire et Cellulaire du Centre National de la
      Recherche Scientifique, UPR 411, 660 Route des Lucioles, Sophia Antipolis, 06560 
      Valbonne, France.
FAU - Dumanchin, C
AU  - Dumanchin C
FAU - Barelli, H
AU  - Barelli H
FAU - Warter, J M
AU  - Warter JM
FAU - Brice, A
AU  - Brice A
FAU - Campion, D
AU  - Campion D
FAU - Frebourg, T
AU  - Frebourg T
FAU - Checler, F
AU  - Checler F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Recombinant Proteins)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Age of Onset
MH  - Alzheimer Disease/*genetics
MH  - Amino Acid Substitution
MH  - Amyloid beta-Peptides/*biosynthesis/genetics
MH  - Amyloid beta-Protein Precursor/biosynthesis/*genetics
MH  - Cell Line
MH  - Female
MH  - Humans
MH  - Male
MH  - Methionine
MH  - Mutagenesis, Site-Directed
MH  - Pedigree
MH  - Phenotype
MH  - *Point Mutation
MH  - Recombinant Proteins/biosynthesis
MH  - Transfection
MH  - Valine
PMC - PMC22430
EDAT- 1999/03/31 00:00
MHDA- 1999/03/31 00:01
CRDT- 1999/03/31 00:00
PHST- 1999/03/31 00:00 [pubmed]
PHST- 1999/03/31 00:01 [medline]
PHST- 1999/03/31 00:00 [entrez]
AID - 10.1073/pnas.96.7.4119 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4119-24. doi: 10.1073/pnas.96.7.4119.