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Table 1 Summary of the effect of the main LOAD-associated variants on microglia phenotypes and in AD

From: TREM2/PLCγ2 signalling in immune cells: function, structural insight, and potential therapeutic modulation

Variant Microglia phenotype AD Clinical phenotype Further comment
PLCγ2 p.P522R Improved survival, increased inflammatory responses [35], reduction of cholesterol ester accumulation,
Increased phagocytosis [36]
Protection against AD [1], DLB and FTD [9], promotion of healthy ageing [9], slower rate of cognitive decline [8], mitigation of tau pathology in presence of amyloid [8] Indirect measurements on BMDMs and BV2 cells [35].
Studies carried out on IPSC-derived microglia-like cells [34]
TREM2 p.R47H Impaired myeloid cell response to plaque in vivo and reduced proliferation [37], increased expression of pro-inflammatory cytokines [38], reduced cell adhesion and altered surface levels observed in iPSC-derived macrophages [39] Not clear
Shown by [40] to increase apraxia, psychiatric and parkinsonian symptoms when compared to non-carriers, but no differences in clinical phenotype observed by [41]
In non-symptomatic carriers, elderly individuals show poor cognitive function [42]). There seems to be too few studies with carriers vs non carriers to draw clear conclusions about the contribution of this variant to disease.
TREM2 p.Q33X Loss of TREM2 expression [43], no studies into effect on microglia phenotype Heterozygous carriers show typical AD pathology with brain atrophy [44] Found in FTD patients [44]
TREM2 p.H157Y Increased shedding from microglia [45], leading to phagocytosis deficits [46] Results in an increased risk of Alzheimer’s disease, but the clinical phenotype is not characterised [47]  
TREM2 p.R62H Impaired phagocytosis of Abeta [17] Unclear due to rarity of this variant