Table 3.
Extracted risk genes for late-onset Alzheimer disease.
| Locus | Gene | Function | References |
|---|---|---|---|
| 12p13.31 | A2M | Alpha2-macroglobulin: cytokine transporter, Abeta degradation with LRP1, interaction with MPO | [654] |
| 21q22.3 | ABCG1 | ATP binding cassette subfamily G member 1 | [275, 276, 655, 656] |
| 18p11.32 | ADCYAP1 | Adenylate cyclase activating polypeptide 1: proprotein increasing cyclic adenosine monophosphate (cAMP) levels, stress response | [656] |
| 10q25.2 | ADRA2A | Adrenoceptor alpha 2A: sympathetic transmission | [657, 658] |
| 10q25.3 | ADRB1 | Adrenoceptor beta 1: sympathetic transmission | [376] |
| 5q31-32 | ADRB2 | Adrenoceptor beta 2: sympathetic transmission | [381] |
| 8p11.23 | ADRB3 | Adrenoceptor beta 3: sympathetic transmission | [659] |
| 6p21.32 | AGER | Advanced glycosylation endproduct (AGE) receptor: neuroinflammation | [660] |
| 10q11.21 | ALOX5 | Arachidonate 5-lipoxygenase: regulator of gamma-secretase | [661] |
| 4p14-p13 | APBB2 | Amyloid beta precursor protein binding family B member 2: Abeta cascade | [275, 276, 662] |
| 21q21.3 | APP | Amyloid beta precursor protein: Abeta cascade | [663] |
| 8q24.3 | ARC | Activity-regulated cytoskeleton-associated protein: synaptic plasticity, regulator of Notch | [664] |
| 12q23.2 | ASCL1/MASH1 | Achaete-scute family bHLH transcription factor 1: ANS neurogenesis, noradrenergic neurons | [665] |
| 22q13.1 | ATF4 | Activating transcription factor 4: neurodegenerative signal | Not tested |
| 20p13 | AVP | Arginine vasopressin: neuropeptide implicated in stress | Not tested |
| 11q23.3 | BACE1 | Beta-secretase 1: Abeta cascade | [666, 667] |
| 19q13.33 | BAX | BCL2 associated X apoptosis regulator: interacting with mitochondrial voltage-dependent anion channel (VDAC) | [668] |
| 3q26.1 | BCHE | Butyrylcholinesterase: cholinergic transmission, acetylcholine catabolism | [275, 276] |
| 11p14.1 | BDNF | Brain-derived neurotrophic factor: age of onset | [669, 670] |
| 17q21.31 | BECN1 | Beclin 1: autophagy | Not tested |
| 5q32 | CAMK2A | Calcium/calmodulin dependent protein kinase II alpha: synaptic plasticity, LTP | [671] |
| 17q12 | CCL2 | C-C motif chemokine ligand 2: immune | Negative finding |
| 17q12 | CCL3 | C-C motif chemokine ligand 3: immune | Negative finding |
| 17q4 | CCL4 | C-C motif chemokine ligand 4: immune | Negative finding |
| 10q21.2 | CDK1 | Cyclin-dependent kinase: cell cycle control, haplotype with p38α, JNK1-3, MEK2, and ERK2 loci | [671] |
| 7q36.1 | CDK5 | Cyclin-dependent kinase: brain development | [275, 276, 612] |
| 17q21.2 | CNP | 2',3'-Cyclic-nucleotide 3'-phosphodiesterase: oligodendrocyte differentiation, microtubule formation | [672] |
| 22q11.2 | COMT | Catechol-O-methyltransferase: catecholamine regulation | Negative finding |
| 2q33.3 | CREB1 | cAMP response element binding protein 1: transcription induction | Not tested |
| 9p13.3 | CREB3 | cAMP response element binding protein 3: transcription induction | Not tested |
| 11p11.2 | CREB3L1 | cAMP responsive element binding protein 3 like 1: ER stress | Not tested |
| 7q33 | CREB3L2 | cAMP responsive element binding protein 3 like 1: ER stress | Not tested |
| Locus | Gene | Function | References |
| 19p13.3 | CREB3L3 | cAMP responsive element binding protein 3 like 1: ER stress | Not tested |
| 1q21.2 | CREB3L4 | cAMP responsive element binding protein 3 like 1: ER stress | Not tested |
| 7p15.1-p14.3 | CREB5 | cAMP response element binding protein 5: trans-activator | Not tested |
| 16p13.3 | CREBBP | CREB binding protein: chromatin remodelling to transcription factor recognition | Not tested |
| 8q13.1 | CRH1 | Corticotropin releasing hormone: HPA | Not tested |
| 5q13.3 | CRHBP | Corticotropin releasing hormone binding protein: CRH inactivation | Not tested |
| 17q21.31 | CRHR1 | Corticotropin releasing hormone receptor 1: HPA regulation, association with MAPT H1 haplotype | [673] |
| 7p14.3 | CRHR2 | Corticotropin releasing hormone receptor 2: HPA regulation | Not tested |
| 1q23.2 | CRP | C-reactive protein: inflammation | [674] |
| 18q21.1 | CTIF | Cap binding complex dependent translation initiation factor: translation | [675] |
| 16q21 | CX3CL1 | C-X3-C motif chemokine ligand 1: fractalkine | Not tested |
| 3p22.2 | CX3CR1 | C-X3-C motif chemokine receptor 1 | Not tested |
| 9q34.2 | DBH | Dopamine beta-hydroxylase: noradrenalin converter, interaction with IL1A and IL6 | [386] |
| 16p12.1 | DCTN5 | Dynactin subunit 5: vesicle transport | Not tested |
| 1q23.3 | DDR2 | Discoidin domain receptor tyrosine kinase 2: cell-environment communication | [675] |
| 1p32.3 | DHCR24 | 24-dehydrocholesterol reductase: cholesterol biosynthesis | [275, 276, 620] |
| 17p13.1 | DLG4 | Discs large MAGUK scaffold protein 4: postsynaptic density protein 95 | [676] |
| 19q13.2 | DNMT1 | DNA methyltransferase 1: maintaining methylation patterns | [92, 677] |
| 2p23.2 | DNMT3A | DNA methyltransferase 3A: de novo methylation | [678] |
| 20q11.21 | DNMT3B | DNA methyltransferase 3B: de novo methylation | [679] |
| 5q35.1 | DUSP1 | Dual specificity phosphatase 1: cellular response to environmental stress | Not tested |
| 21q22.13 | DYRK1A | Dual specificity tyrosine phosphorylation regulated kinase 1A: brain maturation | [275, 276, 680] |
| 11p13 | EAAT2/SLC1A2 | Excitatory amino acid transporter 2/glial high affinity glutamate transporter: synaptic glutamate clearance | [583, 681] |
| 6p24.1 | EDN1 | Endothelin 1: vasoconstrictor | [682] |
| 4q31.22-23 | EDNRA | Endothelin receptor type A: vasoconstriction | Not tested |
| 13q22.3 | EDNRB | Endothelin receptor type B: vasoconstriction | Not tested |
| 5q31.2 | EGR1 | Early growth response 1: transcriptional regulator | [683] |
| 2p22.2 | EIF2AK2 | Eukaryotic translation initiation factor 2 alpha kinase 2: translation initiation | [253, 684] |
| 15q15.1 | EIF2AK4 | Eukaryotic translation initiation factor 2 alpha kinase 4: protein synthesis | [602] |
| 14q23.3 | EIF2S1 | Eukaryotic translation initiation factor 2 subunit alpha: protein synthesis initiation | Not tested |
| 12p13.33 | FKBP4 | FK506 binding protein 4: steroid receptor signalling, immunoregulatory gene expression, tauopathy | [685] |
| 6p21.31 | FKBP5 | FK506 binding protein 5: immunosuppression, calcineurin inhibition, tauopathy, LOAD progression | [686] |
| 14q24.3 | FOS | Fos proto-oncogene AP-1 transcription factor subunit: proliferation, apoptosis | [687] |
| 11q14.1 | GAB2 | Growth factor receptor-bound protein 2 associated binding protein 2: interaction receptor tyrosine kinases, PI3K/ERK/Akt pathway, brain growth | [688-690] |
| Locus | Gene | Function | References |
| 6p21.3 | GABBR1 | Gamma-aminobutyric acid type B receptor subunit 1: inhibitory neurotrans-mission | Not tested |
| 9q22.33 | GABBR2 | Gamma-aminobutyric acid type B receptor subunit 2: inhibitory neurotrans-mission | Not tested |
| 5q34 | GABRA1 | Gamma-aminobutyric acid type A receptor alpha1 subunit: inhibitory neurotrans- mission | Not tested |
| 2q31.2 | GAD1 | Glutamate decarboxylase 1: GABA synthesis | Negative |
| 10p12.1 | GAD65 | Glutamate decarboxylase 2: GABA synthesis | [691] |
| 5p13.2 | GDNF/GDNFOS | Glial cell derived neurotrophic factor: activation of SMAD family transcription factors, neuroprotection | [692] |
| 1p35.3 | GMEB1 | Glucocorticoid modulatory element binding protein 1: transactivation of GRs bound to GREs | [12] |
| 20q13.33 | GMEB2 | Glucocorticoid modulatory element binding protein 2: transactivation of GRs bound to GREs | [12] |
| 12p13.31 | GNB3 | Guanine nucleotide-binding protein subunit beta 3: regulators of signal transduction receptors, interacting with ADRB1/MAPK signalling in LOAD | [376] |
| 5q33.1 | GRIA1 | Glutamate ionotropic receptor AMPA type subunit 1: excitatory neurotransmission | Not tested |
| 4q32.1 | GRIA2 | Glutamate ionotropic receptor AMPA type subunit 2: excitatory neurotransmission | [693] |
| Xq25 | GRIA3 | Glutamate ionotropic receptor AMPA type subunit 3: excitatory neurotransmission | Not tested |
| 11q22.3 | GRIA4 | Glutamate ionotropic receptor AMPA type subunit 4: excitatory neurotransmission | [694] |
| 12p12 | GRIN2B | Glutamate ionotropic receptor NMDA type subunit 2B: ROS, excitotoxicity, excessive Ca++ influx, interacting with ADRA1A | [695] |
| 6q24.3 | GRM1 | Glutamate metabotropic receptor 1: glutamatergic neurotransmission, activation of ERK1/2, LTD/LTP | Not tested |
| 11q14.2-3 | GRM5 | Glutamate metabotropic receptor 5: glutamatergic neurotransmission, receptor for cellular prion protein PrPC bound soluble Abeta42 oligomers | [696, 697] |
| 17q21.31 | GRN | Granulin precursor progranulin: regulating cell growth | [698, 699] |
| 19q13.2 | GSK3A | Glycogen synthase kinase 3 alpha: regulating transcription factor JUN, Wnt/PI3K/signalling, Abeta cascade | Not tested |
| 3q13.33 | GSK3B | Glycogen synthase kinase 3 beta: regulating transcription factor JUN, Wnt/PI3K/signalling, energy metabolism, neuronal cell development, Abeta cascade | [275, 276, 700, 701] |
| 2q31.1 | HAT1 | Histone acetyltransferase 1: rapid acetylation of newly synthesised cytoplasmic histones | [586, 589] |
| 6q21 | HDAC2 | Histone deacetylase 2: deacetylation of lysine residues at histones, transcriptional repression, transcription factor activation | [702] |
| 7p21.1 | HDAC9 | Histone deacetylase 9: recruitment of multi-component co-repressor complexes | [586, 589] |
| 14q23.2 | HIF1A | Hypoxia inducible factor 1 alpha subunit: regulating cellular response to hypoxia, Abeta cascade | [233, 703] |
| 7q34 | HIPK2 | Homeodomain-interacting protein kinase 2: transcription factor, interaction with HIF1A, Abeta cascade | [704] |
| Locus | Gene | Function | References |
| 13q12.3 | HMGB1 | High mobility group box 1: regulating transcription, neuroinflammation, interaction with AGER, Abeta cascade | [705] |
| 5q13.3 | HMGCR | 3-hydroxy-3-methylglutaryl-CoA reductase: rate-limiting enzyme for cholesterol synthesis | [541, 706-708] |
| 20q13.12 | HNF4A | Hepatocyte nuclear factor 4 alpha: nuclear transcription factor, insulin signalling | Negative finding |
| 1q32-q41 | HSD11B1 | Hydroxysteroid 11-beta dehydrogenase 1: cortisol converter enzyme | [12] |
| 16q22.1 | HSD11B2 | Hydroxysteroid 11-beta dehydrogenase 2: cortisol converter enzyme | Negative finding |
| 6q21.31 | HSPA1A | Heat shock protein family A (Hsp70) member 1A: chaperone heat shock protein, trigger of neuronal apoptosis, caspase activation | [346] |
| 12p12.1 | IAPP | Islet amyloid polypeptide amylin: regulating blood glucose levels, brain insulin resistance, rs73069071 related to SLCO1A2 | [210] |
| 12q23.2 | IGF1 | Insulin like growth factor 1: mediating growth and development | [709] |
| 15q26.3 | IGF1R | Insulin like growth factor 1 receptor: anti-apoptotic agent, enhancing cell survival signaling neuroprotection, healthy ageing | [710, 711] |
| 11p15.5 | IGF2 | Insulin like growth factor 2: mediating growth and development, overlap with INS-IGF2 | [712] |
| 6q25.3 | IGF2R | Insulin like growth factor 2 receptor: activation of TGFbeta, degrading IGF2, covariation with WM disintegrity | [634] |
| 7p12.3 | IGFBP1 | Insulin like growth factor binding protein 1: binding both IGFs, mediating interaction with cell surface receptors | [712] |
| 1q32.1 | IL10 | Interleukin 10: anti-inflammatory cytokine produced by monocytes, anti-inflamma- tory reflex, interaction with TNFA and CYP19A1 | [713, 714] |
| 3q25.33 | IL12A | Interleukin 12A: cytokine receptor, induction of IFNgamma | [715, 716] |
| 11q23.1 | IL18 | Interleukin 18: pro-inflammatory cytokine, augmenting killer cell, stimulation IFNgamma | [716] |
| 2q14.1 | IL1A | Interleukin 1A: pro-apoptotic proprotein, interaction with DBH and IL6 attributed to LC neuron loss | [386] |
| 2q14.1 | IL1B | Interleukin 1B: pro-inflammatory response cytokine, mediated by caspase-1, induction of COX-2 | [716] |
| 9p24.1 | IL33 | Interleukin 33: induction of TH2-cells, activation of NFkappaB and MAPK pathways, histone binding | [717] |
| 5q31.1 | IL4 | Interleukin 4: adaptive immunity, chronic inflammation, mediating neurodegeneration, regeneration cascade through effector STAT6, interacting with TREM2 and TYROBP | [651, 718] |
| 7p15.3 | IL6 | Interleukin 6: cytokine both pro- and anti-inflammatory, activating PI3K pathway, targeting PKB, activating DNMT1/DNMT3A/DNMT3B/HDAC1 | [716, 718] |
| 11p15.5 | INS | Insulin: binding to the insulin receptor stimulates glucose uptake, overlap with INS-IGF2 | [719, 720] |
| 11p15.5 | INS-IGF2 | INS-IGF2 read-through: activating ERK and MAPK pathways | [712] |
| 19p13.2 | INSR | Insulin receptor: activating insulin signalling pathway, covariation with WM disintegrity | [634] |
| 1q23.1 | INSRR | Insulin receptor related receptor: activating insulin signalling pathway, covariation with WM disintegrity | [634] |
| 19q13.33 | IRF3 | Interferon regulatory factor 3: transcription factor, forming complex with CREBBP | [721] |
| Locus | Gene | Function | References |
| 2q36.3 | IRS1 | Insulin receptor substrate 1: signal transduction from INSR and IGF1R to PI3K/Akt and ERK/MAPK pathways, related to Beclin-1 | [462] |
| 13q34 | IRS2 | Insulin receptor substrate 1: mediating effects of insulin, insulin-like growth factor 1, cytokines, interacting with IL4 | Not tested in humans |
| 7q32.1 | LEP | Leptin: secreted by white adipocytes, regulation of immune functions and inflammatory responses, interaction with IAPP |
Not tested |
| 12q13.3 | LRP1/APOER | LDL receptor related protein 1: alpha 2-macroglobulin-mediated clearance of Abeta, reducing LOAD risk in APOE epsilon4 carriers | [722, 723] |
| 2q31.1 | LRP2 | LDL receptor related protein 2 megalin: reuptake of lipoproteins and hormones, MAPK signalling and JNK interacting proteins | [724] |
| 19q13.12 | MAG | Myelin-associated glycoprotein: mediating certain myelin-neuron interactions, myelination process | [682, 725, 726] |
| 2q21.1 | MANI | Family with sequence similarity 168 member B: myelin-associated neurite-outgrowth inhibitor, differentiation into catecholaminergic neurons | [726] |
| 5q13.2 | MAP1B | Microtubule associated protein 1B: microtubule assembly, neurogenesis, tauopathy | [727] |
| 16q24.2 | MAP1LC3A/B | Microtubule associated proteins 1 light chain 3 alpha/beta: cytoskeleton interaction, neurogenesis, tauopathy | [728] |
| 6q23.3 | MAP3K5 | Mitogen-activated protein kinase kinase kinase 5: activation of JNK/SAPK | [729] |
| 22q11.22 | MAPK1 | Mitogen-activated protein kinase 1 ERK2: neuronal proliferation, differentiation, transcription regulation | [671] |
| 22q13.11 | MAPK11 | Mitogen-activated protein kinase 11 p38beta: neuronal development | Not tested |
| 22q13.3 | MAPK12 | Mitogen-activated protein kinase 12 p38gamma: signal transducer | Not tested |
| 6p21 | MAPK13 | Mitogen-activated protein kinase 12 p38delta: microtubule dynamics regulator | [271] |
| 6p21.31 | MAPK14 | Mitogen-activated protein kinase 12 p38alpha: stress related transcription, genotoxic stress response | [349, 671] |
| 16p11.2 | MAPK3 | Mitogen-activated protein kinase 3 ERK1: neuronal proliferation | Not tested |
| 10q11.22 | MAPK8 | Mitogen-activated protein kinase 8 JNK1: mediating immediate-early gene expression, co-induction of apoptosis with TNFalpha | [671, 730] |
| 11p11.2 | MAPK8IP1 | Mitogen-activated protein kinase 8 interacting protein 1 JIP1: regulator of JNK1 mediated activation of transcription factors | [302, 303, 731] |
| 16p13.3 | MAPK8IP3 | Mitogen-activated protein kinase 8 interacting protein 2 JIP2: regulator of JNK1 mediated activation of transcription factors | Not tested |
| 5q35.3 | MAPK9 | Mitogen-activated protein kinase 2 JNK2: mediating immediate-early gene expression | [730] |
| 18q21.2 | MBD2 | Methyl-CpG binding domain protein 2: mediator of the biological consequences of the methylation signal | Not tested |
| 18q23 | MBP | Myelin basic protein: major myelin constituent | [725, 732] |
| 18p11.2 | MC2R | Melanocortin 2 receptor: ACTH signalling | [12] |
| Xq28 | MECP2 | Methyl-CpG binding protein 2: binding to methylated DNA | Not tested |
| 22q13.1 | MGAT3 | Mannosyl (beta-1,4-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase: glycosyltransferase, Abeta phagocytosis | [733] |
| 6p22.1 | MOG | Myelin oligodendrocyte glycoprotein: oligodendrocyte surface and outermost of myelin sheath surface, maintenance | [725, 726] |
| Locus | Gene | Function | References |
| 7q22 | MPO | Myeloperoxidase: myeloid differentiation, interacting with A2M | [654] |
| 8p22 | MSR1 | Macrophage scavenger receptor 1: mediating endocytosis of LDLs | [734] |
| 1p36.22 | MTHFR | Methylenetetrahydrofolate reductase: rate-limiting enzyme in the methyl cycle, methylation homeostasis | [92, 735] |
| 11q12.2 | MYRF | Myelin regulatory factor: directly promoting myelin gene expression | Not tested |
| 17q21.1 | NBR1 | Autophagy cargo receptor: autophagic degradation of peroxisomes | Not tested |
| 8q13.3 | NCOA2 | Nuclear receptor coactivator 2: transcriptional coactivator for nuclear hormone receptors | [736] |
| 16q12.2 | NET/SLC6A2 | Solute carrier family 6 member 2: noradrenaline reuptake | [737, 738] |
| 5q23-31 | NEUROG1 | Neurogenin 1: regulating neuronal differentiation, interacting with CREBBP | Not tested |
| 4q25 | NEUROG2 | Neurogenin 2: controlling cortical neuron migration | [739] |
| 10q21.3 | NEUROG3 | Neurogenin 3: transcription factor involved in neurogenesis, determinative for pancreatic islet cell phenotype | Negative finding |
| 4q24 | NFKB1 | Nuclear factor kappa B subunit 1 p50: transcription regulator, neuroinflammation | [740, 741] |
| 10q24.32 | NFKB2 | Nuclear factor kappa B subunit 2: transcription regulator, neuroinflammation | [741] |
| 14q13.3 | NFKBIA | NFKB inhibitor alpha: anti-inflammatory reflex protein | [740, 741] |
| 2q37.1 | NGEF | Neuronal guanine nucleotide exchange factor ephexin: Abeta cascade | [742] |
| 17p13.2 | NLRP1 | NLR family pyrin domain containing 1: neuronal inflammasome, mediating apoptosis, interaction with caspase-2 and caspase-9 | [509, 743, 744] |
| 1q44 | NLRP3 | NLR family pyrin domain containing 3: neuronal inflammasome, mediating apoptosis, upstream activator of NFkappaB signalling | [266, 509, 744] |
| 7q36.1 | NOS3 | Nitric oxide synthase 3: reactive free radical, neurotransmission | [745] |
| 9q34.3 | NOTCH1 | Notch 1: EGF-related, neuropil development | [711] |
| 4q32.2 | NPY1R | Neuropeptide Y receptor Y1: mobilisation of intracellular calcium, neuroprotection | Not tested |
| 5q31.3 | NR3C1 | Nuclear receptor subfamily 3 group C member 1 glucocorticoid receptor: transcription factor, binding to glucocorticoid response elements | [746] |
| 9q33.3 | NR5A1 | Nuclear receptor subfamily 5 group A member 1: transcription factor | Not tested |
| 7q32.2 | NRF1 | Nuclear respiratory factor 1: mitochondrial biogenesis pathway, transcription factor, neurite outgrowth, correlation with PGC-1a | [296, 747] |
| 2q31.2 | NRF2 | Nuclear respiratory factor 2: transcription factor, oxidative stress | [748] |
| 9q21.33 | NTRK2 | Neurotrophic receptor tyrosine kinase 2: binding neurotrophins, signalling in MAPK pathway, neuronal differentiation | [749] |
| Xq23 | NXT2 | Nuclear transport factor 2 like export factor 2: mRNA nuclear export | [675] |
| 12q24.31 | P2RX7 | Purinergic receptor P2X 7: formation of membrane pores | [750] |
| 20q13.31 | PCK1 | Phosphoenolpyruvate carboxykinase 1: regulation of gluconeogenesis through insulin, glucocorticoids | [751] |
| 2p11.2 | PERK | Eukaryotic translation initiation factor 2 alpha kinase 3: modulating mitochondrial function, ER stress | [602] |
| 7q11.23 | PION | Gamma-secretase activating protein: increasing Abeta production, interaction with gamma-secretase and APP-CTF | [752] |
| Locus | Gene | Function | References |
| 19p13.12 | PKN1 | Protein kinase N1: mediating insulin signalling, tauopathy | [753] |
| Xq22.2 | PLP1 | Proteolipid protein: transmembrane protein, myelin compaction, maintenance, interacting with EDN1 | [682, 725] |
| 11q13 | PP1 | Protein phosphatase 1: hepatic blood-glucose levels, glycogen metabolism | [754] |
| 3p25.2 | PPARG | Peroxisome proliferator activated receptor gamma: adipocyte differentiation, T2DM | Negative |
| 4p15.1 | PPARGC1A | PPARG coactivator 1 alpha: regulation of CREB and NRFs, neuronal cholesterol homeostasis | [296, 747] |
| 5q32 | PPARGC1B | PPARG coactivator 1 beta: non-oxidative glucose metabolism, regulating transcription factors and glucocorticoid receptor | [755] |
| 1p36.33 | PRKCZ | Protein kinase zeta: stabilisation of LTP, atypical isoform: insulin stimulated glucose transport, consistent with memory loss | [459, 460] |
| 17p13.1 | PSD95/DLG4 | Postsynaptic density protein 95, LTP | [756] |
| 14q24.1 | PSEN1 | Presenilin 1: regulating APP processing, cleavage of Notch receptor | Negative |
| 1q42.13 | PSEN2 | Presenilin 2: regulating APP processing, cleavage of Notch receptor | Negative |
| 14q22.1 | PTGER2 | Prostaglandin E receptor 2: glial cells, neuroinflammation, GSK-3beta, beta-catenin signalling, COX-2 induction | [757] |
| 1p31.1 | PTGER3 | Prostaglandin E receptor 3: reducing cAMP-dependent signalling, COX-2 induction | [515] |
| 5p13.1 | PTGER4 | Prostaglandin E receptor 4: activating transcription factor CREP signalling, EGR-1 expression through ERK, p38, PI3K/Akt/mTOR pathways | [758] |
| 9q33.2 | PTGS1 | Prostaglandin-endoperoxide synthase 1 COX-1: catalysing prostaglandin biosynthesis | [759] |
| 1q31.1 | PTGS2 | Prostaglandin-endoperoxide synthase 1 COX-2: inducible isozyme, prostanoid biosynthesis, neuroinflammation | [760, 761] |
| 11p15.1 | PTPN5 | Protein tyrosine phosphatase, non-receptor type 5 STEP: dephosphorylation of ERK1/2, p38, internalisation of NMDARs, synaptic strength | [762] |
| 16p11.2 | PYCARD | PYD and CARD domain containing: apoptotic signalling pathway, activation of caspase | [763] |
| 6p23 | RANBP9 | RAN binding protein 9: translocation of RNA, Abeta cascade | [764] |
| 21q22.1 | RCAN1 | Regulator of calcineurin 1: inhibiting calcineurin-dependent signalling pathways, CNS development, activation of caspase-3, linking tau and Abeta | [765] |
| 7q22.1 | RELN | Reelin: neurogenesis, synaptic positioning, LTP, interaction with CDK5, GSK-3b, interaction with APP | [766] |
| 4q12 | REST | RE1 silencing transcription factor: neuron-restrictive silencer element, master negative regulator of neurogenesis | Not tested |
| 12q24.31 | SCARB1 | Scavenger receptor class B member 1: HDL receptor | Negative |
| 4q21.1 | SCARB2 | Scavenger receptor class B member 2: lyosomal membranes | Not tested |
| 7q11.2 | SCARB3 | Scavenger receptor class B member 3 CD36: fatty acid transport | [767] |
| 14q32.13 | SERPINA3 | Serpin family A member 3: plasma protease inhibitor | [768] |
| 17q11.2 | SERT/SLC6A4 | Solute carrier family 6 member 4: serotonin transporter | Negative |
| 6q23.2 | SGK1 | Serum/glucocorticoid regulated kinase 1: anti-apoptotic cellular stress protector, Akt homologue | [769] |
| Locus | Gene | Function | References |
| 1q22 | SH3GLB1 | Endophilin-B1: Bax-interacting factor 1 Bif-1 | [194] |
| 1q21.2 | SHC1 | SHC adaptor protein 1: mitochondrial matrix, ROS regulator | [770] |
| 12p12.1 | SLCO1A2 | Hepatic solute carrier organic anion transporter family member 1A2: uptake bile acids, steroidal compounds, interacting with IAPP | [210] |
| 4q22.1 | SNCA | Alpha synuclein: presynaptic terminals | [771] |
| 1q25.2 | SOAT1 | Sterol O-acyltransferase 1: cholesterol acyltransferase, endoplasmic reticulum, cholesterol equilibrium, Abeta cascade | [275, 276] |
| 21q22.1 | SOD1 | Superoxide dismutase 1: ROS converter | [772] |
| 10q25.1 | SORCS1 | Sortilin related VPS10 domain containing receptor 1: covariation with WM disintegrity | [634, 773] |
| 11q24.1 | SORL1 | Sortilin related receptor 1: neuronal LDL receptor, covariation with WM disintegrity | [634, 773] |
| 17q21.2 | STAT3 | Signal transducer and activator of transcription 3: respondent to cytokines and growth factors | [741] |
| Xp11.23 | SYP | Synaptophysin: binding cholesterol, targeting of vesicle-associated synaptobrevin | Not tested |
| 6q27 | TBP | TATA-box binding protein: element of transcription factor IID (TFIID) | [774] |
| 10q21.1 | TFAM | Mitochondrial transcription factor A: mitochondrial DNA replication and repair | [296, 775] |
| 12q13.12-13 | TFCP2 | Transcription factor CP2: binding the alpha-globin promoter, inflammatory response | [776] |
| 6p21 | TFEB | Transcription factor EB: lyosomal biogenesis, autophagy, activated by PGC-1alpha | Not tested |
| 19q13.2 | TGFB1 | Transforming growth factor beta 1: regulating cell proliferation, and growth, covariation with WM disintegrity | [634, 777] |
| 9q33.1 | TLR4 | Toll like receptor 4: activation of innate immunity | [778] |
| 6p21.33 | TNFA | Tumor necrosis factor alpha: cytokine, cell proliferation, apoptosis, neuroinflammation | [779] |
| 8p21.2 | TNFRSF10A | TNF receptor superfamily member 10A: inducing cell apoptosis | [780] |
| 8p21.2 | TNFRSF10B | TNF receptor superfamily member 10B: transducing apoptosis signal | [780] |
| 12p13.31 | TNFRSF1A | TNF receptor superfamily member 1A: inhibiting inflammation | [781] |
| 1p36.22 | TNFRSF1B | TNF receptor superfamily member 1B: mediating anti-apoptotic signals, anti-oxidative pathways, neuroprotection | Negative finding |
| 13q14.11 | TNFSF11 | TNF superfamily member 11 RANKL: regulation of cell apoptosis | [782] |
| Xq22.3 | TSC22D3 | TSC22 domain family member 3: anti-inflammatory protein glucocorticoid (GC)-induced leucine zipper, immunosuppression through NFkappaB | Not tested |
| 12q24.33 | ULK1 | Unc-51 like autophagy activating kinase 1: autophagy regulator | Not tested |
| 5q31.1 | VDAC1 | Voltage dependent anion channel 1: metabolite exchange in mitochondria | [217, 783] |
| 6p21.1 | VEGFA | Vascular endothelial growth factor A: embryonic blood vessel formation, metabolic abnormalities | [784] |
| 9p24.2 | VLDLR | Very low density lipoprotein receptor: VLDL-triglyceride metabolism, reelin signalling pathway | [785, 786] |
Method remarks: This table contains suspected gene loci extracted from preceding text sections, based on animal research, and suspected risk genes from additional literature. These loci were tested for associations in human LOAD genetic studies in PubMed and/or AlzGene databases. If not available, human pathophysiology studies are reported instead.