Table 1.
A summary of inflammation-related genes located on HSA21.
| Gene | Protein | Function | References | Present in common DS mouse models# | AD risk identified in GWAS@ |
|---|---|---|---|---|---|
| ABCG1 | ATP binding cassette subfamily G member 1 | Catalyzes phospholipid and cholesterol efflux and maintains macrophages in an anti-inflammatory state. | Wojcik et al. (2008) | Dp17, Tc1 | Wollmer et al. (2007) and Beecham et al. (2014) |
| ADAMTS1 | ADAM metallopeptidase with thrombospondin type 1 motif 1. | Secreted protease is known to be induced by IL-1β. | Kuno et al. (1997) | Dp16, Ts65Dn, Tc1 | Kunkle et al. (2019), Niu et al. (2019), and Tan et al. (2021) |
| ADAMTS5 | ADAM metallopeptidase with thrombospondin type 1 motif 5. | Secreted protease known to be induced by IL-1β and TGFβ. | Yamanishi et al. (2002) | Dp16, Ts65Dn, Tc1 | none |
| APP | Amyloid beta precursor protein | Neuronal acute phase protein precursor of Aβ fragments in Alzheimer’s plaques and inducer of IL-1β. | Glenner and Wong (1984), Tanzi et al. (1988), and Barger and Harmon (1997) | Dp16, Ts65Dn, Tc1* | Guyant-Maréchal et al. (2007), Nowotny et al. (2007), and Lv et al. (2008) |
| BACE2 | Beta-secretase 2 | Cleaves APP for less Aβ and increases IL-1R2, a decoy proteinfor excess IL-1 capture. | Kuhn et al. (2007) | Dp16, Ts65Dn, Tc1 | Myllykangas et al. (2005) |
| CBS | Cystathionine beta-synthase | Catalyzes production of hydrogen sulfide bimodalregulation of inflammation. | Sen et al. (2011) | Dp17, Tc1 | Beyer et al. (2004) |
| CSTB | Cystatin B | Thiol protease inhibitor involved in Aβ clearance. | Yang et al. (2011) and Maher et al. (2014) | Dp10, Tc1 | Kurt et al. (2020) |
| CXADR | CXADR Ig-like cell adhesion molecule | Activation of JNK and p38-MAPK pathways leading toproduction of M1 cytokines. | Yuen et al. (2011) | Dp16, Tc1 | none |
| DYRK1A | Dual specificity tyrosine phosphorylation regulated kinase 1A | Serine/threonine and tyrosine kinase that regulates the NFκB pathway and phosphorylates tau. | Latour et al. (2019) | Dp16, Ts65Dn, Tc1 | Kimura et al. (2007) |
| IFNAR1 | Interferon alpha and beta receptor subunit 1 | Activates JAK/STAT mediated anti-inflammatory pathway. | Kim et al. (1997) | Dp16, Ts65Dn | Patel et al. (2021) |
| IFNAR2 | Interferon alpha and beta receptor subunit 2 | Activates JAK/STAT mediated anti-inflammatory pathway. | Kim et al. (1997) and Boselli et al. (2010) | Dp16, Ts65Dn | none |
| IFNGR2 | Interferon gamma receptor 2 | Activates JAK/STAT mediated anti-inflammatory pathway. | Boselli et al. (2010) | Dp16, Ts65Dn | none |
| PRMT2 | Protein arginine methyltransferase 2 | Blocks the actions of NFκB in the nucleus. | Ganesh et al. (2006) | Dp10, Tc1$ | none |
| RCAN1 | Regulator of calcineurin 1 | Inhibits calcineurin-dependent transcription and is regulated by STAT2. | Lee et al. (2012) | Dp16, Ts65Dn | Lin et al. (2011) |
| RIPK4 | Receptor interacting serine/threonine kinase 4 | Necessary for signaling through TNF receptor 1. | Rountree et al. (2010) | Dp16, Ts65Dn, Tc1 | none |
| RUNX1 | RUNX family transcription factor 1 | Transcription factor regulating T-cell function. | Tang et al. (2018) | DP16, Ts65Dn, Tc1& | Kimura et al. (2007) and Patel et al. (2011) |
| S100B | S100 calcium binding protein B | Upregulates IL-1β and APP expression, released in responseto TNFα. | Li et al. (1998), Liu et al. (2005), and Donato et al. (2013) | Dp10, Tc1$ | Lambert et al. (2007) |
| SOD1 | Superoxide dismutase 1 | Scavenges superoxide radicals producing H2O2 and O2. | Danciger et al. (1986) | Dp16, Ts65Dn, Tc1 | none |
| TIAM1 | TIAM Rac1 associated GEF 1 | Necessary for cytokine-mediated generation of oxidativespecies through NADPH oxidase. | Subasinghe et al. (2011) | Dp16, Ts65Dn, Tc1 | none |
Some parts of Table 1 are reproduced from Wilcock and Griffin (2013) with permission under the CC BY 2.0 license (http://creativecommons.org/licenses/by/2.0/), Copyright © Wilcock and Griffin (2013); licensee BioMed Central Ltd. Abbreviations: Aβ, β-amyloid; ADAM, a disintegrin and metalloprotease; APP, amyloid beta precursor protein; ATP, adenosine triphosphate; CXADR, coxsackievirus and adenovirus receptor; DS, Down syndrome; IL, interleukin; GEF, guanine nucleotide exchange factor; GWAS, genome-wide associate study; MAPK, mitogen-activated protein kinase; NADPH, Nicotinamide adenine dinucleotide phosphate; RUNX, Runt-related transcription factor; TNF, tumor necrosis factor; TGF, transforming growth factor; JAK/STAT, Janus kinase signal transducer and activator of transcription; JNK, c-Jun N-terminal kinase; TIAM, T-cell lymphoma invasion and metastasis; TNFR, tumor necrosis factor receptor; NFκB, Nuclear factor-kappa B; STAT2, signal transducer and activator of transcription 2. #Tc1 mice express one copy of the human gene and two copies of the homologous mouse gene, while Ts65Dn, Dp10, Dp16, and Dp17 mice express three copies of the homologous mouse gene, as identified in Ahmed et al. (2013). *In Tc1 mice, the APP gene is re-arranged, and therefore human APP is not functionally expressed. $In Tc1 mice, the human PRMT2 and S100B genes are duplicated, in addition to two copies of the homologous mouse genes. &In Tc1 mice, the human RUNX1 gene is partially deleted. @Some relevant GWAS studies were identified using the AlzGene database (Bertram et al., 2007).