Abstract
Alzheimer's disease is an important public concern with rising prevalence across the
globe. While many therapeutic approaches for Alzheimer's disease have been developed,
there are currently no validated disease-modifying treatments. Thus, in order to develop
novel treatment strategies, there is a significant need to progress our understanding
of the pathogenesis of Alzheimer's disease. Several large genome-wide association
studies and whole genome and exome sequencing studies have identified novel genes
associated with late-onset Alzheimer's disease. Interestingly, many of the genes are
associated with inflammation and the immune system, including complement receptor
1, clusterin, CD33, EPH receptor A1, membrane-spanning 4-domains subfamily A, ATP-binding
cassette sub-family A member 7, major histocompatibility complex class II, inositol
polyphosphate-5-phosphatase, myocyte enhancer factor 2C, and triggering receptor expressed
on myeloid cells 2. The pathogenetic contributions of immune reaction and neuroinflammation
in Alzheimer's disease have been regarded largely as part of amyloid cascade hypothesis.
The neurotoxic amyloid-β (Aβ) induces activation of immune cells, such as microglia,
astrocytes, perivascular macrophages and lymphocytes and decreased capability of clearing
Aβ by immune system and chronic inflammation caused by activated immune cells aggravate
neuronal damage and eventually Alzheimer's disease. But the precise mechanism and
hereditary impact on such process is largely unknown. The current findings in genetic
studies suggest that the immunological mechanisms of Alzheimer's disease may extend
beyond passive reaction of Aβ, including the development of Alzheimer's disease such
as time of onset and rate of progression. In this article, we aimed to review the
mechanisms of immune reaction and neuroinflammation in Alzheimer's disease, with an
emphasis on the function of genes known to be associated with a risk of Alzheimer's
disease in terms of neuroinflammation and immune function.
Keywords
Alzheimer’s disease - neuroinflammation - immune - microglia - genetics
