PMID- 7806491
OWN - NLM
STAT- MEDLINE
DCOM- 19950130
LR  - 20210212
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 269
IP  - 52
DP  - 1994 Dec 30
TI  - APP717 missense mutation affects the ratio of amyloid beta protein species (A 
      beta 1-42/43 and a beta 1-40) in familial Alzheimer's disease brain.
PG  - 32721-4
AB  - We have biochemically purified A beta from brains of two unrelated familial 
      Alzheimer's disease (FAD) pedigrees with the APP717 mutation (Val-->Ile) and from 
      two sporadic Alzheimer's disease (AD) brains and characterized them by means of 
      mass spectrometry and enzyme-linked immunosorbent assay. We observed two types of 
      amyloid beta protein (A beta), the short-tail form (A beta 1-40) and the 
      long-tail form (A beta 1-42/43), in sporadic AD and FAD brains, and found that 
      the ratio of the long-tail form of A beta (A beta 1-42/43) to total A beta was 
      increased in FAD brains. These in vivo results were confirmed in vitro using 
      cultured cells transfected with three kinds of APP cDNAs bearing the APP717 
      mutations (Val-->Ile, Gly, or Phe). Taken together with the hypothesis that A 
      beta 1-42/43 functions as a "seed" that increases the kinetics of amyloid fibril 
      formation (Jarrett, J. T., and Lansbury, P. T., Jr. (1993) Cell 73, 1055-1058), 
      we conclude that the APP717 missense mutation does not create new A beta species 
      but promotes the increased accumulation of A beta 1-42/43 in the brain, which 
      results in the enhancement of amyloid fibril formation from soluble A beta. These 
      findings provide a causal relationship between this FAD genotype and the 
      pathological phenotype of A beta deposition and senile plaque formation.
FAU - Tamaoka, A
AU  - Tamaoka A
AD  - Department of Neurology, University of Tsukuba, Ibaraki, Japan.
FAU - Odaka, A
AU  - Odaka A
FAU - Ishibashi, Y
AU  - Ishibashi Y
FAU - Usami, M
AU  - Usami M
FAU - Sahara, N
AU  - Sahara N
FAU - Suzuki, N
AU  - Suzuki N
FAU - Nukina, N
AU  - Nukina N
FAU - Mizusawa, H
AU  - Mizusawa H
FAU - Shoji, S
AU  - Shoji S
FAU - Kanazawa, I
AU  - Kanazawa I
AU  - et al.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (APP717)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 0 (amyloid beta-protein (1-42))
SB  - IM
MH  - Adult
MH  - Alzheimer Disease/*genetics/metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Brain/*metabolism
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Peptide Fragments/*metabolism
EDAT- 1994/12/30 00:00
MHDA- 1994/12/30 00:01
CRDT- 1994/12/30 00:00
PHST- 1994/12/30 00:00 [pubmed]
PHST- 1994/12/30 00:01 [medline]
PHST- 1994/12/30 00:00 [entrez]
AID - S0021-9258(20)30050-8 [pii]
PST - ppublish
SO  - J Biol Chem. 1994 Dec 30;269(52):32721-4.