%0 Journal Article
%T The Innate Immune System in Alzheimer¡¯s Disease
%A Allal Boutajangout
%A Thomas Wisniewski
%J International Journal of Cell Biology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/576383
%X Alzheimer¡¯s disease (AD) is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloid ¦Â (A¦Â) peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA) and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT). Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4) (Potter and Wisniewski (2012), and Verghese et al. (2011)). Recently, it has been reported by two groups independently that a rare functional variant (R47H) of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs) and are the resident macrophages of the central nervous system (CNS). In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD. 1. Introduction Alzheimer¡¯s disease is the most common cause of dementia globally [1]. AD is characterized by the presence of amyloid ¦Â (A¦Â) deposits in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA) as well as aggregated tau protein in the form of neurofibrillary tangles (NFT). These lesions are associated with neuronal loss and synaptic damage, which produce the cognitive dysfunction which characterizes AD. Mutations in three genes have been shown to cause early-onset AD (EOAD): the amyloid precursor protein (APP), Presenilin 1 (PS1), and Presenilin 2 (PS2) [2, 3]. Mutations associated with these genes affect <1% of all AD patients and are not informative regarding the causes of the much more common late-onset AD (LOAD) [2, 3]. Inheritance of the apolipoprotein E (ApoE4) allele is the major genetic risk factor that is associated with late onset AD [4, 5]. Several environmental factors are known as risk factors for LOAD including, aging, head trauma, type 2 diabetes, hypertension, hypercholesterolemia, and vascular pathology [6]. Recently, two independent groups of investigators have identified a rare variant in the gene encoding the triggering receptor expressed on myeloid cells 2 protein (TREM2), which is predicted to result in a R47H substitution that causes an ~3-fold increase in the susceptibility to LOAD. Although the odds ratio
%U http://www.hindawi.com/journals/ijcb/2013/576383/