PMID- 1906990
OWN - NLM
STAT- MEDLINE
DCOM- 19910828
LR  - 20220310
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 352
IP  - 6332
DP  - 1991 Jul 18
TI  - Formation of beta-amyloid protein deposits in brains of transgenic mice.
PG  - 239-41
AB  - Deposits of beta-amyloid are one of the main pathological characteristics of 
      Alzheimer's disease. The beta-amyloid peptide constituent (relative molecular 
      mass 4,200) of the deposits is derived from the beta-amyloid precursor protein 
      (beta-APP) which is expressed in several different isoforms. The two most 
      prevalent beta-APP isoforms are distinguished by either the presence 
      (beta-APP751) or absence (beta-APP695) of a Kunitz serine protease inhibitor 
      domain. Changes in the abundance of different beta-APP messenger RNAs in brains 
      of Alzheimer's disease victims have been widely reported. Although these results 
      have been controversial, most evidence favours an increase in the mRNAs encoding 
      protease inhibitor-containing isoforms of beta-APP and it is proposed that this 
      change contributes to beta-amyloid formation. We have now produced an imbalance 
      in the normal neuronal ratio of beta-APP isoforms by preparing transgenic mice 
      expressing additional beta-APP751 under the control of a neural-specific 
      promoter. The cortical and hippocampal brain regions of the transgenic mice 
      display extracellular beta-amyloid immunoreactive deposits varying in size (less 
      than 5-50 microns) and abundance. These results suggest that one mechanism of 
      beta-amyloid formation may involve a disruption of the normal ratio of neuronal 
      beta-APP isoform expression and support a direct relationship between increased 
      expression of Kunitz inhibitor-bearing beta-APP isoforms and beta-amyloid 
      deposition.
FAU - Quon, D
AU  - Quon D
AD  - California Biotechnology Inc., Mountain View 94043.
FAU - Wang, Y
AU  - Wang Y
FAU - Catalano, R
AU  - Catalano R
FAU - Scardina, J M
AU  - Scardina JM
FAU - Murakami, K
AU  - Murakami K
FAU - Cordell, B
AU  - Cordell B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (Protein Precursors)
SB  - IM
MH  - Alzheimer Disease/*genetics
MH  - Amyloid beta-Peptides/analysis/biosynthesis/*genetics
MH  - Amyloid beta-Protein Precursor
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Western
MH  - Brain/*metabolism
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Oligonucleotide Probes
MH  - Protein Precursors/analysis/biosynthesis/*genetics
EDAT- 1991/07/18 00:00
MHDA- 1991/07/18 00:01
CRDT- 1991/07/18 00:00
PHST- 1991/07/18 00:00 [pubmed]
PHST- 1991/07/18 00:01 [medline]
PHST- 1991/07/18 00:00 [entrez]
AID - 10.1038/352239a0 [doi]
PST - ppublish
SO  - Nature. 1991 Jul 18;352(6332):239-41. doi: 10.1038/352239a0.