Alzheimer's disease-associated complement gene variants influence plasma complement protein levels.

Background: Alzheimer's disease (AD) has been associated with immune dysregulation in biomarker and genome-wide association studies (GWAS). GWAS hits include the genes encoding complement regulators clusterin (CLU) and complement receptor 1 (CR1), recognised as key players in AD pathology, and complement proteins have been proposed as biomarkers.

Main Body: To address whether changes in plasma complement protein levels in AD relate to AD-associated complement gene variants we first measured relevant plasma complement proteins (clusterin, C1q, C1s, CR1, factor H) in a large cohort comprising early onset AD (EOAD; n = 912), late onset AD (LOAD; n = 492) and control (n = 504) donors.

Complement dysregulation and Alzheimer's disease in Down syndrome.

Introduction: Down syndrome (DS) is associated with immune dysregulation and a high risk of early onset Alzheimer's disease (AD). Complement is a key part of innate immunity and driver of pathological inflammation, including neuroinflammation in AD. Complement dysregulation has been reported in DS; however, the pattern of dysregulation and its relationship to AD risk is unclear.