Angiotensin-converting enzyme levels and activity in Alzheimer's disease: differences in brain and CSF ACE and association with ACE1 genotypes

作者：Miners Scott^*; Ashby Emma; Baig Shabnam; Harrison Rachel; Tayler Hannah; Speedy Elizabeth; Prince Jonathan A; Love Seth; Kehoe Patrick G

来源：American Journal of Translational Research, 2009, 1(2): 163-177.

• Angiotensin-converting enzyme
• enzyme activity
• Braak stage
• ACE1
• Alzheimer's disease
• cerebrospinal fluid
• neuron-specific enolase

Angiotensin-converting enzyme (ACE) has been implicated in Alzheimer's disease (AD): ACE1 variations influence plasma ACE and risk of AD, and ACE is increased in AD brain. We measured frontal ACE level and activity in 89 AD and 51 control brains, and post-mortem CSF from 101 cases and 19 controls. Neuron-specific enolase (NSE) level and Braak stage were used to indicate neuronal preservation and disease progression. We genotyped the common ACE insertion/deletion polymorphism, rs4343, rs1800764 and rs4921. ACE activity was elevated in AD and correlated with Braak stage. Crude ACE levels were unchanged but adjustment for NSE suggested increased neuronal ACE production with Braak stage. Exposing SH-SY-5Y neurons to oligomeric A beta 1-42 increased ACE level and activity, suggesting A beta may upregulate ACE in AD. In CSF, ACE level but not activity was reduced in AD. ACE1 genotype did not predict ACE level or activity in brain or CSF. ACE activity and neuronal production increase in AD brain, possibly in response to A beta. Peripheral measurements do not reflect ACE activity in the brain.

• 出版日期2009