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Complement component 3 and complement factor H protein levels are altered in brain tissues from people with human
Jerel Adam Fields1, Mary Swinton1, Erin E Sundermann1
1Department of Psychiatry, University of California, San Diego, San Diego, CA, United States.
Frontiers in Aging Neuroscience
|September 19, 2022
Summary
People with HIV (PWH) experience central nervous system dysfunction, including HIV-associated neurocognitive disorder (HAND). This study found increased complement component 3 (C3) in the brain, linked to Alzheimer's disease pathology and cognitive deficits in PWH.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- People with HIV (PWH) often develop central nervous system dysfunction, such as HIV-associated neurocognitive disorder (HAND), even with effective treatment.
- Aging PWH are also susceptible to age-related neurodegenerative diseases like Alzheimer's disease (AD), which involves beta-amyloid (Aβ) plaques and neuroinflammation.
- The complement system, particularly complement component 3 (C3) and its regulator complement factor H (CFH), plays a role in AD pathogenesis and neurological dysfunction in PWH.
Purpose of the Study:
- To investigate the relationship between brain levels of C3 and CFH, Aβ plaque deposition, and neurological dysfunction in people with HIV.
- To analyze C3 and CFH protein levels in specific brain regions (frontal cortex and cerebellum) and correlate them with cognitive performance in PWH.
Main Methods:
- Analysis of C3 and CFH protein levels in frontal cortex and cerebellum brain specimens from 22 PWH using immunoblotting.
- Correlation of measured C3 and CFH protein levels with pre-existing data on Aβ plaque deposition and cognitive function in the PWH cohort.
Main Results:
- Significantly increased C3 protein levels were observed in the frontal cortex of PWH with Aβ plaques and HAND compared to controls.
- C3 levels trended higher in the cerebellum of brains with Aβ plaques.
- C3 protein levels were higher in the frontal cortex than the cerebellum, while CFH levels were higher in the cerebellum than the frontal cortex. CFH in the frontal cortex correlated with executive function and motor performance.
Conclusions:
- Elevated C3 in the frontal cortex is associated with Aβ plaques and HAND in PWH.
- Regional differences in C3 and CFH distribution exist in the PWH brain.
- These findings support the role of complement system proteins in the neuropathogenesis of HAND and AD in people with HIV.
