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Nat Rev Immunol. 2018 Aug 23. doi: 10.1038/s41577-018-0051-1. [Epub ahead of print]

Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight.

Author information

1
Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
2
Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA. holtzman@wustl.edu.

Abstract

Alzheimer disease is more than a pure proteopathy. Chronic neuroinflammation stands out during the pathogenesis of the disease and in turn modulates disease progression. The central nervous system (CNS) is separated from the blood circulation by the blood-brain barrier. In Alzheimer disease, neuroinflammation heavily relies on innate immune responses that are primarily mediated by CNS-resident microglia. APOE (which encodes apolipoprotein E) is the strongest genetic risk factor for Alzheimer disease, and APOE was recently shown to affect the disease in part through its immunomodulatory function. This function of APOE is likely linked to triggering receptor expressed on myeloid cells 2 (TREM2), which is expressed by microglia in the CNS. Here, we review the rapidly growing literature on the role of disease-associated microglia, TREM2 and APOE in the pathogenesis of Alzheimer disease and present an integrated view of innate immune function in Alzheimer disease.

PMID:
30140051
DOI:
10.1038/s41577-018-0051-1

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