科研之友
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摘要
Age-dependent accumulation of the amyloid-beta peptide (A beta) in the brain is a pre-condition for development of Alzheimers disease. A relative increase in the generation of longer A beta species such as A beta 42 and A beta 43 is critical for A beta deposition, but the underlying mechanism remains unresolved. Here, we performed a cell-free assay using microsome fractions of temporal cortex tissues from 42 cynomolgus monkeys and found that A beta 40-generating ?-secretase activity (?40) decreased with age, whereas A beta 42-generating ?-secretase activity (?42) was unaltered. In ELISAs, more than 80% of monkeys over 20-years old showed evidence of A beta accumulation in the temporal cortex. The ratio of ?42 to ?40 increased with age and correlated with the level of accumulated A beta. These results suggest that ?-secretase activity undergoes age-related, non-genetic modulation and that this modulation may cause A beta accumulation in aging brains. Similar modulation may predispose aged human brains to Alzheimers disease.
- 出版日期2012-10
