Abstract
Genetic evidence has supported a protective effect of cerebral
angiotensin converting enzyme (ACE) against Alzheimer’s disease (AD).
However, it is unclear whether this is mediated through blood pressure
and extends to other neurodegenerative diseases. We performed genetic
colocalization investigating an effect of cortical ACE expression
on AD risk. We further investigated whether any effect of ACEexpression is mediated through changes in blood pressure, and whether
effects extend to Parkinson’s disease, small vessel disease or cognitive
function. There was genetic evidence supporting a protective effect of
cortical ACE expression on AD risk. Although higher corticalACE expression was associated with higher blood pressure, there
was no strong evidence to support that its association with AD was
mediated through blood pressure, nor that ACE expression affected
risk of other neurodegenerative traits. Genetic evidence supports
protective effects of cerebral ACE expression on AD, but not other
neurodegenerative outcomes.