Format

Send to

Choose Destination
Exp Gerontol. 2018 Jul 1;107:59-66. doi: 10.1016/j.exger.2017.12.019. Epub 2017 Dec 21.

Role of the peripheral innate immune system in the development of Alzheimer's disease.

Author information

1
Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada.
2
Department of Biochemistry, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada.
3
Department of Infectious Diseases and Microbiology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada.
4
A*STAR, Singapore Immunology Network, Biopolis, Singapore.
5
Department of Internal Medicine II, Center for Medical Research University of Tübingen, Tübingen, Germany; Health Sciences North Research Institute, Sudbury, Ontario, Canada.
6
Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland.
7
Research Center on Aging, Graduate Program in Immunology, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada. Electronic address: Tamas.Fulop@Usherbrooke.ca.

Abstract

Alzheimer's disease is one of the most devastating neurodegenerative diseases. The exact cause of the disease is still not known although many scientists believe in the beta amyloid hypothesis which states that the accumulation of the amyloid peptide beta (Aβ) in brain is the initial cause which consequently leads to pathological neuroinflammation. However, it was recently shown that Aβ may have an important role in defending the brain against infections. Thus, the balance between positive and negative impact of Aβ may determine disease progression. Microglia in the brain are innate immune cells, and brain-initiated inflammatory responses reflected in the periphery suggests that Alzheimer's disease is to some extent also a systemic inflammatory disease. Greater permeability of the blood brain barrier facilitates the transport of peripheral immune cells to the brain and vice versa so that a vicious circle originating on the periphery may contribute to the development of overt clinical AD. Persistent inflammatory challenges by pathogens in the periphery, increasing with age, may also contribute to the central propagation of the pathological changes seen clinically. Therefore, the activation status of peripheral innate immune cells may represent an early biomarker of the upcoming impact on the brain. The modulation of these cells may thus become a useful mechanism for modifying disease progression.

KEYWORDS:

Alzheimer disease; Amyloid beta; Blood brain barrier; Infections; Microglia; NK cells; Neutrophils; Peripheral innate immune system

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center