PMID- 1465129
OWN - NLM
STAT- MEDLINE
DCOM- 19930121
LR  - 20220330
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 360
IP  - 6405
DP  - 1992 Dec 17
TI  - Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease 
      increases beta-protein production.
PG  - 672-4
AB  - Progressive cerebral deposition of the 39-43-amino-acid amyloid beta-protein (A 
      beta) is an invariant feature of Alzheimer's disease which precedes symptoms of 
      dementia by years or decades. The only specific molecular defects that cause 
      Alzheimer's disease which have been identified so far are missense mutations in 
      the gene encoding the beta-amyloid precursor protein (beta-APP) in certain 
      families with an autosomal dominant form of the disease (familial Alzheimer's 
      disease, or FAD). These mutations are located within or immediately flanking the 
      A beta region of beta-APP, but the mechanism by which they cause the pathological 
      phenotype of early and accelerated A beta deposition is unknown. Here we report 
      that cultured cells which express a beta-APP complementary DNA bearing a double 
      mutation (Lys to Asn at residue 595 plus Met to Leu at position 596) found in a 
      Swedish FAD family produce approximately 6-8-fold more A beta than cells 
      expressing normal beta-APP. The Met 596 to Leu mutation is principally 
      responsible for the increase. These data establish a direct link between a FAD 
      genotype and the clinicopathological phenotype. Further, they confirm the 
      relevance of the continuous A beta production by cultured cells for elucidating 
      the fundamental mechanism of Alzheimer's disease.
FAU - Citron, M
AU  - Citron M
AD  - Department of Neurology, Harvard Medical School, Boston, Massachusetts.
FAU - Oltersdorf, T
AU  - Oltersdorf T
FAU - Haass, C
AU  - Haass C
FAU - McConlogue, L
AU  - McConlogue L
FAU - Hung, A Y
AU  - Hung AY
FAU - Seubert, P
AU  - Seubert P
FAU - Vigo-Pelfrey, C
AU  - Vigo-Pelfrey C
FAU - Lieberburg, I
AU  - Lieberburg I
FAU - Selkoe, D J
AU  - Selkoe DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Oligodeoxyribonucleotides)
SB  - IM
MH  - Alzheimer Disease/*genetics/metabolism
MH  - Amino Acid Sequence
MH  - Amyloid beta-Peptides/*biosynthesis
MH  - Amyloid beta-Protein Precursor/*genetics
MH  - Base Sequence
MH  - Cell Line
MH  - Humans
MH  - Kidney
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Oligodeoxyribonucleotides
MH  - Restriction Mapping
MH  - Sweden
MH  - Transfection
EDAT- 1992/12/17 00:00
MHDA- 1992/12/17 00:01
CRDT- 1992/12/17 00:00
PHST- 1992/12/17 00:00 [pubmed]
PHST- 1992/12/17 00:01 [medline]
PHST- 1992/12/17 00:00 [entrez]
AID - 10.1038/360672a0 [doi]
PST - ppublish
SO  - Nature. 1992 Dec 17;360(6405):672-4. doi: 10.1038/360672a0.