UC San Diego

People with HIV (PWH) continue to suffer from dysfunction of the central nervous system, as evidenced by HIV-associated neurocognitive disorder (HAND), despite antiretroviral therapy and suppressed viral loads. As PWH live longer they may also be at risk of age-related neurodegenerative diseases such Alzheimer's disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). The complement system is associated with deposition of AD-related proteins such as beta amyloid (Aβ), neuroinflammation, and neurological dysfunction in PWH. Complement component 3 (C3) is a key protagonist in the complement cascade and complement factor H (CFH) is an antagonist of C3 activity. We investigated the relationship between C3 and CFH levels in the brain and Aβ plaques and neurological dysfunction in 22 PWH. We analyzed by immunoblot C3 and CFH protein levels in frontal cortex (FC) and cerebellum (CB) brain specimens from PWH previously characterized for Aβ plaque deposition. C3 and CFH protein levels were then correlated with specific cognitive domains. C3 protein levels in the FC were significantly increased in brains with Aβ plaques and in brains with HAND compared to controls. In the CB, C3 levels trended higher in brains with Aβ plaques. Overall C3 protein levels were significantly higher in the FC compared to the CB, but the opposite was true for CFH, having significantly higher levels of CFH protein in the CB compared to the FC. However, only CFH in the FC showed significant correlations with specific domains, executive function and motor performance. These findings corroborate previous results showing that complement system proteins are associated with HAND and AD neuropathogenesis.