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 ACE expression 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 cortical ACE 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.