Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer’s disease

Abstract

Microglia have been identified as key players in Alzheimer's disease pathogenesis, and other neurodegenerative diseases. Iba1, and more specifically TMEM119 and P2RY12 are gaining ground as presumedly more specific microglia markers, but comprehensive characterization of the expression of these three markers individually as well as combined is currently missing. Here we used a multispectral immunofluorescence dataset, in which over seventy thousand microglia from both aged controls and Alzheimer patients have been analysed for expression of Iba1, TMEM119 and P2RY12 on a single-cell level. For all markers, we studied the overlap and differences in expression patterns and the effect of proximity to β-amyloid plaques. We found no difference in absolute microglia numbers between control and Alzheimer subjects, but the prevalence of specific combinations of markers (phenotypes) differed greatly. In controls, the majority of microglia expressed all three markers. In Alzheimer patients, a significant loss of TMEM119+ phenotypes was observed, independent of the presence of β-amyloid plaques in its proximity. Contrary, phenotypes showing loss of P2RY12, but consistent Iba1 expression were increasingly prevalent around β-amyloid plaques. No morphological features were conclusively associated with loss or gain of any of the markers or any of the identified phenotypes. All in all, none of the three markers were expressed by all microglia, nor can be wholly regarded as a pan- or homeostatic marker, and preferential phenotypes were observed depending on the surrounding pathological or homeostatic environment. This work could help select and interpret microglia markers in previous and future studies.

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice

“…Chymase, a serine protease in mast cells, were also increased in the HDM group compared to the intranasal PBS control group. To further explore the role of other immune cells that are potentially activated during allergic lung inflammation and can play a role in brain inflammation, we measured expression of Iba-1 protein, a microglial marker whose expression is generally higher in activated microglia [53]. Microglia are a type of macrophage in the brain whose increase in number is associated with brain inflammation.…”

Deep proteomic analysis of microglia reveals fundamental biological differences between model systems

“…3b). Although a lack of microglia marker protein expression could suggest a lack of microglia identity, it may also represent an activated microglia phenotype, as both P2RY12 and TMEM119 are downregulated in microglia in response to inflammatory stimuli (Zrzavy 2017) and neurodegeneration (Keren-Shaul 2017, Krasemann 2017, Kenkhuis 2022). Indeed, microglia/macrophage phagocytosis marker CD68 is expressed in all four microglia subsets, supporting a microglia identity in each, however expression is drastically higher in BV2 microglia suggestive of activation (Fig.…”

Effects of Electroacupuncture on the Correlation between Serum and Central Immunity in AD Model Animals

“…Iba-1, a marker of activation microglia, was widely used to identify immunopositivity microglia in a number of central nervous system disorders, such as Alzheimer's disease [51], schizophrenia and bipolar disorder [52,53], and spinal cord injury [54,55]. Not only did we confirm that Iba-1 was significantly expressed in SAMP8 mice but we also discovered that the expression of Iba-1 in the hippocampus and frontal lobe was proven to be positively connected to the blood levels of IL-6 and IL-1β.…”