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J Immunol. 2020 Jan 15;204(2):306-315. doi: 10.4049/jimmunol.1901068.

Complement-Mediated Events in Alzheimer's Disease: Mechanisms and Potential Therapeutic Targets.

Tenner AJ1,2,3,4.

Author information

1
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA 92697; atenner@uci.edu.
2
Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA 92697; atenner@uci.edu.
3
Department of Pathology and Laboratory Medicine, School of Medicine, University of California Irvine, Irvine, CA 92697; and atenner@uci.edu.
4
Institute for Memory Impairment and Neurological Disorders, University of California Irvine, Irvine, CA 92697 atenner@uci.edu.

Abstract

An estimated 5.7 million Americans suffer from Alzheimer's disease in the United States, with no disease-modifying treatments to prevent or treat cognitive deficits associated with the disease. Genome-wide association studies suggest that an enhancement of clearance mechanisms and/or promotion of an anti-inflammatory response may slow or prevent disease progression. Increasing awareness of distinct roles of complement components in normal brain development and function and in neurodegenerative disorders align with complement-mediated responses, and thus, thorough understanding of these molecular pathways is needed to facilitate successful therapeutic design. Both beneficial and detrimental effects of C1q as well as contributions to local inflammation by C5a-C5aR1 signaling in brain highlight the need for precision of therapeutic design. The potential benefit of β-amyloid clearance from the circulation via CR1-mediated mechanisms is also reviewed. Therapies that suppress inflammation while preserving protective effects of complement could be tested now to slow the progression of this debilitating disease.

PMID:
31907273
PMCID:
PMC6951444
[Available on 2021-01-15]
DOI:
10.4049/jimmunol.1901068

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