Implication of Complement System and its Regulators in Alzheimers Disease

Martin   V.   Kolev; Marieta   M.   Ruseva; Claire   L.   Harris; B.   Paul   Morgan; Rossen   M.   Donev

doi:10.2174/157015909787602805

Abstract

Alzheimers disease (AD) is an age-related neurodegenerative disease that affects approximately 24 million people worldwide. A number of different risk factors have been implicated in AD, however, neuritic (amyloid) plaques are considered as one of the defining risk factors and pathological hallmarks of the disease. Complement proteins are integral components of amyloid plaques and cerebral vascular amyloid in Alzheimer brains. They can be found at the earliest stages of amyloid deposition and their activation coincides with the clinical expression of Alzheimers dementia. This review emphasizes on the dual key roles of complement system and complement regulators (CRegs) in disease pathology and progression. The particular focus of this review is on currently evolving strategies for design of complement inhibitors that might aid therapy by restoring the fine balance between activated components of complement system, thus improving the cognitive performance of patients. This review discusses these issues with a view to inspiring the development of new agents that could be useful for the treatment of AD.

Keywords: Alzheimer's disease, neurodegeneration, inflammation, β-amyloid peptide, complement, complement regulators, CD59, complement therapeutics