ACE variants and association with brain Aβ levels in Alzheimer's disease

ACE is a candidate gene for Alzheimer's disease (AD) and associations have been reported between ACE variants and plasma ACE levels, AD risk, AD age at onset of disease and cerebrospinal fluid levels of A beta. Despite evidence that ACE can degrade A beta, the relationships between ACE variants and the levels of different types of A beta in the brain are not known. We have investigated the relationship between AD-associated ACE variants, for which the associations with brain activity of ACE were previously analysed, and brain homogenate levels of soluble, insoluble and oligomeric A beta. Reported AD risk variants in the ACE indel (rs1799752) and its 'proxy' rs4343 were significantly associated with soluble A beta level in AD only (p=0.001), as was rs1800764 but less so (p=0.014). In contrast, insoluble A beta was associated with ACE indel and rs4343 variants in controls only (p < 0.01). No associations were found for oligomeric A beta. These data indicate a complex relationship between ACE and A beta that differs between AD and control brains.