Expression of transgenic APP mRNA is the key determinant for beta-amyloid deposition in PS2APP transgenic mice.
BACKGROUND
Alzheimer's disease is the most common cause of dementia occurring in the elderly. The identification of the genetic factors in the familial forms of the disease enabled the generation of transgenic animals which reproduce an essential part of its pathology. Various lines of transgenic mice expressing human wild-type or mutated APP have been reported. The phenotype expressed in these mice varies according to the transgene itself, the promoter used for its expression, and the level of expression achieved in the brain, but is also determined by the genetic background of the mice.


METHODS
We analyzed the variability in the amyloid load by ELISA and the levels of huAPP transcripts by quantitative PCR in our PS2APP double-transgenic mice when expressed in a mixed C57Bl/6, DBA/2 background.


RESULTS
In 12-month-old PS2APP double-transgenic mice, the amount of cerebral amyloid deposits is directly correlated with the levels of the huAPP transgenic transcript. Furthermore, a reduction in human APP transcripts by 50% leads to a complete absence of cerebral deposits at the age of 12 months.


CONCLUSIONS
Our results demonstrate that a 2-fold reduction in APP expression can result in a profound decrease in brain pathology.
Ozmen
Laurence
L
Preclinical CNS Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland. Laurence.ozmen@roche.com
Albientz
Anita
A
Czech
Christian
C
Jacobsen
Helmut
H
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000473:pathology; D002878:Chromosomes, Human, Pair 1; D002891:Chromosomes, Human, Pair 21; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D053766:Presenilin-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508861:PSEN2 protein, human; D053766:Presenilin-2; D012333:RNA, Messenger