These data show that BACE1 mRNA expression is under the control of a regulatory noncoding RNA that may drive Alzheimer's disease-associated pathophysiology.
BACE1 activity correlated positively with CSF levels of secreted APP isoforms and Abeta(40) in the AD and control groups and in all MCI subgroups (P < .05) except the MCI subgroup that developed AD.
Through meta-analysis of the Del or G allele by pooling Asian studies, only BACE1-G allele appeared to increase risk of developing Alzheimer's disease.
To examine whether BACE elevation was due to mutations in the BACE-coding region, we sequenced the entire ORF region of the BACE gene in these same AD and nondemented patients and performed allelic association analysis.
Elevated BACE1 expression coupled with increased deposition provides functional evidence for beta-secretase as a primary effector in regional amyloid deposition in the AD brain.
These results suggest that BACE1 gene expression is tightly regulated at the transcriptional level and that the transcription factor Sp1 plays an important role in regulation of BACE1 to process APP generating Abeta in Alzheimer's disease.
We conclude that sequence variation in the BACE1 or BACE 2 gene is not a significant risk factor for AD; however, a combination of a specific BACE1 allele and APOE epsilon 4 may increase the risk for Alzheimer disease over and above that attributed to APOE epsilon 4 alone.
We searched the BACE coding region mutations/polymorphisms of cDNA in 25 AD patients and 100 healthy controls by single-strand conformational polymorphism.
It appears that BACE polymorphism plays a more important role in the development of AD than previously assumed, possibly by influencing Abeta(42) levels.
By comparative Western blot analysis, we show a 2.7-fold increase in protein expression of the beta-secretase enzyme BACE in the brain cortex of Alzheimer's disease patients as compared to age-matched controls.
Immunohistochemical analysis demonstrated that BACE immunoreactivity in the brain was predominantly neuronal and was found in tangle-bearing neurons in AD.