[Re: Whether there is any data correlating ECE levels and age in humans] The simple answer is that it hasn't yet been examined. The regulation of ECE expression is complex, as evidenced by the production of multiple isoforms of both ECE-1 and ECE-2 through the use of multiple promoters and alternative splicing. Thus, a comprehensive approach to examine each of the isoforms may be necessary, and this is now under way in our laboratory. The complex regulation of ECE activity and the influence of ECE on Aβ levels suggests that physiological conditions that cause a reduction in ECE activity in the brain may elevate Aβ levels and increase susceptibility to AD. Reductions in ECE activity in the brain (either in total activity or in the relative expression of ECE isoforms) may occur in normal aging, the most common risk factor for AD. Equally important, however, is the possibility that there may be individuals with normally high levels of ECE activity who are at a reduced risk for the disease. To address these issues we are also examining the ECE expression and enzymatic activity in human brain and determining whether these measures correlate with the amount of soluble and/or insoluble Aβ present in normal individuals, individuals with mild cognitive impairment (MCI), individuals with autopsy-confirmed AD, and individuals with other neurological diseases. You can read more about ECE and Aβ in a recent review of ours, available in preprint form (Chapter 7).
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Mayo Clinic College of Medicne
[Re: Whether there is any data correlating ECE levels and age in humans] The simple answer is that it hasn't yet been examined. The regulation of ECE expression is complex, as evidenced by the production of multiple isoforms of both ECE-1 and ECE-2 through the use of multiple promoters and alternative splicing. Thus, a comprehensive approach to examine each of the isoforms may be necessary, and this is now under way in our laboratory. The complex regulation of ECE activity and the influence of ECE on Aβ levels suggests that physiological conditions that cause a reduction in ECE activity in the brain may elevate Aβ levels and increase susceptibility to AD. Reductions in ECE activity in the brain (either in total activity or in the relative expression of ECE isoforms) may occur in normal aging, the most common risk factor for AD. Equally important, however, is the possibility that there may be individuals with normally high levels of ECE activity who are at a reduced risk for the disease. To address these issues we are also examining the ECE expression and enzymatic activity in human brain and determining whether these measures correlate with the amount of soluble and/or insoluble Aβ present in normal individuals, individuals with mild cognitive impairment (MCI), individuals with autopsy-confirmed AD, and individuals with other neurological diseases. You can read more about ECE and Aβ in a recent review of ours, available in preprint form (Chapter 7).
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