The formation of Alzheimer's Aβ peptide is initiated when the amyloid precursor protein (APP) is cleaved by the enzyme β-secretase (BACE1); inhibition of this cleavage has been proposed as a means of treating Alzheimer's disease. (AD) We have previously shown that young BACE1 knockout mice (BACE1 KO) do not generate Aβ but in other respects appear normal. Here we have extended this analysis to include both gene expression profiling and phenotypic assessment of older BACE1 KO animals to evaluate the impact of chronic Aβ deficiency. We did not detect global compensatory changes in neural gene expression in young BACE1 KO mice. In particular, expression of the β-secretase homolog BACE2 was not upregulated. Furthermore, we found no structural alterations in any organ, including all central and peripheral neural tissues, of BACE1 KO mice up to 14 months of age. Aged BACE1 KO mice engineered to overexpress human APP (BACE1 KO/APPtg) did not develop amyloid plaques. These data provide evidence that neither β-secretase nor Aβ plays a vital role in mouse physiology and that chronic β-secretase inhibition could be a useful approach in treating AD.
|Original language||English (US)|
|Number of pages||8|
|Journal||Neurobiology of Disease|
|State||Published - Jan 1 2003|
- Alzheimer's disease
ASJC Scopus subject areas