LilrB3 is a putative cell surface receptor of APOE4

Zhou, Jiayao; Wang, Yumeng; Huang, Guangli; Yang, Minghong; Zhu, Yumin; Chen, Jin; Jing, Dan; Jiao, Kai; Shi, Yigong

doi:10.1038/s41422-022-00759-y

Cited by 13 publications

(4 citation statements)

References 125 publications

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“…The CSF ABETA and the CSF TAU, respectively, reflect the deposition of amyloid in the cerebral cortex and the density of neurodegeneration, and the CSF PTAU is related to the pathological changes of neurofibrillary tangles. The decreased level of the ABETA and the elevated levels of the TAU and the PTAU are the important CSF features of the AD (Zou et al, 2020).…”

Section: Clinical Phenotypesmentioning

confidence: 99%

“…Among them, APOE , TOMM40 , and LOC100129500 are known to be important genetic risk factors for the AD. More specifically, there are three most common alleles ε2, ε3, and ε4 in the APOE gene, which correspond to three protein isoforms: APOE2 , APOE3 , and APOE4 , respectively ( Safieh et al, 2019 ; Zhou et al, 2023 ). Genetically, the ε4 allele of the APOE gene is the strongest risk factor for the AD ( Liu et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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X chromosome-wide association study of quantitative biomarkers from the Alzheimer’s Disease Neuroimaging Initiative study

Wang,

Yuan,

Zhu

et al. 2023

Front. Aging Neurosci.

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IntroductionAlzheimer’s disease (AD) is a complex neurodegenerative disease with high heritability. Compared to autosomes, a higher proportion of disorder-associated genes on X chromosome are expressed in the brain. However, only a few studies focused on the identification of the susceptibility loci for AD on X chromosome.MethodsUsing the data from the Alzheimer’s Disease Neuroimaging Initiative Study, we conducted an X chromosome-wide association study between 16 AD quantitative biomarkers and 19,692 single nucleotide polymorphisms (SNPs) based on both the cross-sectional and longitudinal studies.ResultsWe identified 15 SNPs statistically significantly associated with different quantitative biomarkers of the AD. For the cross-sectional study, six SNPs (rs5927116, rs4596772, rs5929538, rs2213488, rs5920524, and rs5945306) are located in or near to six genes DMD, TBX22, LOC101928437, TENM1, SPANXN1, and ZFP92, which have been reported to be associated with schizophrenia or neuropsychiatric diseases in literature. For the longitudinal study, four SNPs (rs4829868, rs5931111, rs6540385, and rs763320) are included in or near to two genes RAC1P4 and AFF2, which have been demonstrated to be associated with brain development or intellectual disability in literature, while the functional annotations of other five novel SNPs (rs12157031, rs428303, rs5953487, rs10284107, and rs5955016) have not been found.Discussion15 SNPs were found statistically significantly associated with the quantitative biomarkers of the AD. Follow-up study in molecular genetics is needed to verify whether they are indeed related to AD. The findings in this article expand our understanding of the role of the X chromosome in exploring disease susceptibility, introduce new insights into the molecular genetics behind the AD, and may provide a mechanistic clue to further AD-related studies.

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Section: Clinical Phenotypesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

X chromosome-wide association study of quantitative biomarkers from the Alzheimer’s Disease Neuroimaging Initiative study

Wang,

Yuan,

Zhu

et al. 2023

Front. Aging Neurosci.

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“…Additionally, Apolipoprotein E4 (APOE4) gene variant represents the strongest genetic risk factor for LOAD ( Bellenguez et al, 2022 ). Recently, Zhou et al (2023) identified Leukocyte Immunoglobulin-Like Receptor B3 (LilrB3) as a putative cell surface receptor of APOE4. This ligand-receptor engagement induces a robust IFN-I signature in a human microglia cell line, suggesting a potential mechanism yet to be validated in vivo .…”

Section: Ifn-i In Alzheimer’s Diseasementioning

confidence: 99%

In sickness and in health—Type I interferon and the brain

Cao

2024

Front. Aging Neurosci.

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Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I’s effects on brain aging, Alzheimer’s disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms of neurodegeneration. Understanding the intricate role of IFN-I and its associated pathways in the CNS not only advances our comprehension of brain health and disease but also presents opportunities for developing interventions to modify the process of neurodegeneration and prevent age-related cognitive decline.

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“…Zhou et al [ 95 ] explored the leukocyte immunoglobulin-like receptor B3 (LilrB3) and its immunomodulatory effects in APOE4 versus ε2 and showed that only APOE4, specifically, interacts with LilrB3 and activates human microglia cells (HMC3) into a pro-inflammatory state in a LilrB3-dependent manner.…”

Section: Apoe4 Brain Effectsmentioning

confidence: 99%

APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM2.5 Polluted Cities

Calderón‐Garcidueñas

Hernández-Luna²,

Aiello-Mora

et al. 2023

Biomolecules

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This Review emphasizes the impact of APOE4—the most significant genetic risk factor for Alzheimer’s disease (AD)—on peripheral and neural effects starting in childhood. We discuss major mechanistic players associated with the APOE alleles’ effects in humans to understand their impact from conception through all life stages and the importance of detrimental, synergistic environmental exposures. APOE4 influences AD pathogenesis, and exposure to fine particulate matter (PM2.5), manufactured nanoparticles (NPs), and ultrafine particles (UFPs) associated with combustion and friction processes appear to be major contributors to cerebrovascular dysfunction, neuroinflammation, and oxidative stress. In the context of outdoor and indoor PM pollution burden—as well as Fe, Ti, and Al alloys; Hg, Cu, Ca, Sn, and Si UFPs/NPs—in placenta and fetal brain tissues, urban APOE3 and APOE4 carriers are developing AD biological disease hallmarks (hyperphosphorylated-tau (P-tau) and amyloid beta 42 plaques (Aβ42)). Strikingly, for Metropolitan Mexico City (MMC) young residents ≤ 40 y, APOE4 carriers have 4.92 times higher suicide odds and 23.6 times higher odds of reaching Braak NFT V stage versus APOE4 non-carriers. The National Institute on Aging and Alzheimer’s Association (NIA-AA) framework could serve to test the hypothesis that UFPs and NPs are key players for oxidative stress, neuroinflammation, protein aggregation and misfolding, faulty complex protein quality control, and early damage to cell membranes and organelles of neural and vascular cells. Noninvasive biomarkers indicative of the P-tau and Aβ42 abnormal protein deposits are needed across the disease continuum starting in childhood. Among the 21.8 million MMC residents, we have potentially 4 million APOE4 carriers at accelerated AD progression. These APOE4 individuals are prime candidates for early neuroprotective interventional trials. APOE4 is key in the development of AD evolving from childhood in highly polluted urban centers dominated by anthropogenic and industrial sources of pollution. APOE4 subjects are at higher early risk of AD development, and neuroprotection ought to be implemented. Effective reductions of PM2.5, UFP, and NP emissions from all sources are urgently needed. Alzheimer’s Disease prevention ought to be at the core of the public health response and physicians-scientist minority research be supported.

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LilrB3 is a putative cell surface receptor of APOE4

Cited by 13 publications

References 125 publications

X chromosome-wide association study of quantitative biomarkers from the Alzheimer’s Disease Neuroimaging Initiative study

X chromosome-wide association study of quantitative biomarkers from the Alzheimer’s Disease Neuroimaging Initiative study

In sickness and in health—Type I interferon and the brain

APOE Peripheral and Brain Impact: APOE4 Carriers Accelerate Their Alzheimer Continuum and Have a High Risk of Suicide in PM2.5 Polluted Cities

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