ArticlePLoS genetics2018
Paired Immunoglobulin-like Type 2 Receptor Alpha G78R variant alters ligand binding and confers protection to Alzheimer's disease.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 3 syntheses or guidelines pooled it, 87 citations in OpenAlex.
- Manifestations of Alzheimer's disease genetic risk in the blood are evident in a multiomic analysis in healthy adults aged 18 to 90.Scientific reports · 2022Pooled it
- Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer's disease risk genes.Nature genetics · 2021Pooled it
- Interpretation of risk loci from genome-wide association studies of Alzheimer's disease.The Lancet. Neurology · 2020Pooled it
- Proteome-wide Mendelian randomisation of lung function to identify potential therapeutic targets for respiratory disease.ERJ open research · 2026Article
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- Long-term temporal stability of circulating proteins in older adults.Nature communications · 2026Article
- Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.Nature reviews. Drug discovery · 2026Review
- Can we refute a role for infections in Alzheimer's disease pathogenesis?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Human CSF proteogenomics links genetic variation to neurodegenerative disease proteins.medRxiv : the preprint server for health sciences · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Association between pre-diagnostic prevalence of 30 common diseases and the subsequent risk of dementia: a population-based retrospective cohort study in Taiwan.Frontiers in aging neuroscience · 2026Article
- Genetic insights into drug targets for alzheimer's disease: integrative multi-omics analysis.Alzheimer's research & therapy · 2025Article
- Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.Nature aging · 2025Article
- Prefusion structure, evasion and neutralization of HSV-1 glycoprotein B.Nature microbiology · 2025Article
- Long-term temporal stability of circulating proteins in older adults.bioRxiv : the preprint server for biology · 2025Article
- Combining GWAS Summary Data and Proteomics Identified Potential Drug Targets in Dementia.Molecular neurobiology · 2025Article
- PILRα on tumor cells interacts with the T cell surface protein CD99 to suppress antitumor immunity.Nature cancer · 2025Article
- Alzheimer's disease and age-related macular degeneration: Shared and distinct immune mechanisms.Immunity · 2025Review
- Ramp Sequence May Explain Synonymous Variant Association with Alzheimer's Disease in the Paired Immunoglobulin-like Type 2 Receptor Alpha (PILRA).Biomedicines · 2025Article
- Biomarker identification for Alzheimer's disease through integration of comprehensive Mendelian randomization and proteomics data.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Paired Immunoglobulin-like Type 2 Receptor Alpha (PILRA) is a cell surface inhibitory receptor that recognizes specific O-glycosylated proteins and is expressed on various innate immune cell types including microglia. We show here that a common missense variant (G78R, rs1859788) of PILRA is the likely causal allele for the confirmed Alzheimer's disease risk locus at 7q21 (rs1476679). The G78R variant alters the interaction of residues essential for sialic acid engagement, resulting in >50% reduced binding for several PILRA ligands including a novel ligand, complement component 4A, and herpes simplex virus 1 (HSV-1) glycoprotein B. PILRA is an entry receptor for HSV-1 via glycoprotein B, and macrophages derived from R78 homozygous donors showed significantly decreased levels of HSV-1 infection at several multiplicities of infection compared to homozygous G78 macrophages. We propose that PILRA G78R protects individuals from Alzheimer's disease risk via reduced inhibitory signaling in microglia and reduced microglial infection during HSV-1 recurrence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.