| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Little is known about the ACE activity in the CNS in living patients with AD. We therefore measured ACE activity in CSF in patients with mild cognitive impairment (MCI) and mild-to-moderate AD, and compared them with age-matched healthy controls. We also examined whether treatment by a brain-penetrating ACE inhibitor can alter CSF-ACE activity in patients with mild-to-moderate AD. The mean baseline MMSE value was 18.9 ± 0.7 (SE) in 付he AD group; 25.0 ± 0.4 in the MCI group; and 28.5 ± 0.3 in the normal group. CSF-ACE activity was elevated in the MCI group [0.32 (mean) ± 0.13 (SE) IU/L, n = 20] vs the control group (0.17 ± 0.02 IU/L, n = 20, p < 0.0001). There was also an increase in the mean CSF-ACE activity in the AD group (0.24 ± 0.01 IU/L, n = 34, p = 0.0219) vs the control group. The brain-penetrating ACE inhibitor, perindopril inhibited CSF-ACE activity in patients with AD after 1 month of treatment [0.24 ± 0.02 (before) vs 0.13 ± 0.03 IU/L (after), n = 7, p = 0.038]. There was no significant difference in the concentration of CSF somatostatin among the MCI, AD or control groups. We therefore assume that an increased CNS-ACE activity might be involved in the progression of AD, although the precise mechanism remains unknown. Brain-penetrating ACE inhibitor might provide a protection against progression of AD or MCI.
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