Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362:329–44.
Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chetelat G, Teunissen CE, et al. Alzheimer’s disease. Lancet. 2021;397:1577–90.
Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet. 2019;51:414–30.
Jansen IE, Savage JE, Watanabe K, Bryois J, Williams DM, Steinberg S, et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat Genet. 2019;51:404–13.
Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, et al. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease. Nat Genet. 2021;53:1276–82.
Bellenguez C, Küçükali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, et al. New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat Genet. 2022;54:412–36.
Jia L, Li F, Wei C, Zhu M, Qu Q, Qin W, et al. Prediction of Alzheimer’s disease using multi-variants from a Chinese genome-wide association study. Brain. 2021;144:924–37.
Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, et al. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013;368:117–27.
Zhang DF, Fan Y, Xu M, Wang G, Wang D, Li J, et al. Complement C7 is a novel risk gene for Alzheimer’s disease in Han Chinese. Natl Sci Rev. 2019;6:257–74.
Zhou X, Chen Y, Mok KY, Zhao Q, Chen K, Chen Y, et al. Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis. Proc Natl Acad Sci U S A. 2018;115:1697–706.
Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14:388–405.
Koelink PJ, Overbeek SA, Braber S, de Kruijf P, Folkerts G, Smit MJ, et al. Targeting chemokine receptors in chronic inflammatory diseases: an extensive review. Pharmacol Ther. 2012;133:1–18.
Su F, Bai F, Zhang Z. Inflammatory cytokines and Alzheimer’s disease: a review from the perspective of genetic polymorphisms. Neurosci Bull. 2016;32:469–80.
Savarin-Vuaillat C, Ransohoff RM. Chemokines and chemokine receptors in neurological disease: raise, retain, or reduce? Neurotherapeutics. 2007;4:590–601.
Bajetto A, Bonavia R, Barbero S, Florio T, Schettini G. Chemokines and their receptors in the central nervous system. Front Neuroendocrinol. 2001;22:147–84.
Réaux-Le Goazigo A, Van Steenwinckel J, Rostène W, Mélik PS. Current status of chemokines in the adult CNS. Prog Neurobiol. 2013;104:67–92.
Dziembowska M, Tham TN, Lau P, Vitry S, Lazarini F, Dubois-Dalcq M. A role for CXCR4 signaling in survival and migration of neural and oligodendrocyte precursors. Glia. 2005;50:258–69.
Tsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, et al. The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell. 2002;110:373–83.
Padovani-Claudio DA, Liu L, Ransohoff RM, Miller RH. Alterations in the oligodendrocyte lineage, myelin, and white matter in adult mice lacking the chemokine receptor CXCR2. Glia. 2006;54:471–83.
Bertollini C, Ragozzino D, Gross C, Limatola C, Eusebi F. Fractalkine/CX3CL1 depresses central synaptic transmission in mouse hippocampal slices. Neuropharmacology. 2006;51:816–21.
Da Mesquita S, Herz J, Wall M, Dykstra T, de Lima KA, Norris GT, et al. Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and beta-amyloid pathology. Sci Adv. 2021;7:eabe4601.
Zhou L, Kong G, Palmisano I, Cencioni MT, Danzi M, De Virgiliis F, et al. Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline. Science. 2022;376:eabd5926.
Sokolova A, Hill MD, Rahimi F, Warden LA, Halliday GM, Shepherd CE. Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer’s disease. Brain Pathol. 2009;19:392–8.
Tripathy D, Thirumangalakudi L, Grammas P. RANTES upregulation in the Alzheimer’s disease brain: a possible neuroprotective role. Neurobiol Aging. 2010;31:8–16.
Kauwe JS, Bailey MH, Ridge PG, Perry R, Wadsworth ME, Hoyt KL, et al. Genome-wide association study of CSF levels of 59 alzheimer’s disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation. PLoS Genet. 2014;10:e1004758.
Perea JR, Lleo A, Alcolea D, Fortea J, Avila J, Bolos M. Decreased CX3CL1 levels in the cerebrospinal fluid of patients with Alzheimer’s disease. Front Neurosci. 2018;12:609.
Lee WJ, Liao YC, Wang YF, Lin IF, Wang SJ, Fuh JL. Plasma MCP-1 and cognitive decline in patients with Alzheimer’s disease and mild cognitive impairment: a two-year follow-up study. Sci Rep. 2018;8:1280.
Goldeck D, Larbi A, Pellicano M, Alam I, Zerr I, Schmidt C, et al. Enhanced chemokine receptor expression on leukocytes of patients with Alzheimer’s disease. PLoS ONE. 2013;8:e66664.
Iarlori C, Gambi D, Gambi F, Lucci I, Feliciani C, Salvatore M, et al. Expression and production of two selected beta-chemokines in peripheral blood mononuclear cells from patients with Alzheimer’s disease. Exp Gerontol. 2005;40:605–11.
Jorda A, Cauli O, Santonja JM, Aldasoro M, Aldasoro C, Obrador E, et al. Changes in chemokines and chemokine receptors expression in a mouse model of Alzheimer’s disease. Int J Biol Sci. 2019;15:453–63.
Guedes JR, Santana I, Cunha C, Duro D, Almeida MR, Cardoso AM, et al. MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer’s disease. Alzheimers Dement (Amst). 2016;3:7–17.
Guedes JR, Lao T, Cardoso AL, El Khoury J. Roles of microglial and monocyte chemokines and their receptors in regulating Alzheimer’s disease-associated amyloid-beta and tau pathologies. Front Neurol. 2018;9:549.
Subbarayan MS, Joly-Amado A, Bickford PC, Nash KR. CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases. Pharmacol Ther. 2022;231:107989.
Bhaskar K, Konerth M, Kokiko-Cochran ON, Cardona A, Ransohoff RM, Lamb BT. Regulation of tau pathology by the microglial fractalkine receptor. Neuron. 2010;68:19–31.
Liu Z, Condello C, Schain A, Harb R, Grutzendler J. CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar amyloid-beta phagocytosis. J Neurosci. 2010;30:17091–101.
Kiyota T, Gendelman HE, Weir RA, Higgins EE, Zhang G, Jain M. CCL2 affects beta-amyloidosis and progressive neurocognitive dysfunction in a mouse model of Alzheimer’s disease. Neurobiol Aging. 2013;34:1060–8.
Vendramini AA, de Labio RW, Rasmussen LT, Minett T, Bertolucci PH, de Arruda Cardoso Smith M, et al. Interleukin-8 gene polymorphism -251T>A and Alzheimer’s disease. J Alzheimers Dis. 2007;12:221–2.
Villa C, Venturelli E, Fenoglio C, Clerici F, Marcone A, Benussi L, et al. CCL8/MCP-2 association analysis in patients with Alzheimer’s disease and frontotemporal lobar degeneration. J Neurol. 2009;256:1379–81.
Balistreri CR, Grimaldi MP, Vasto S, Listi F, Chiappelli M, Licastro F, et al. Association between the polymorphism of CCR5 and Alzheimer’s disease: results of a study performed on male and female patients from Northern Italy. Ann N Y Acad Sci. 2006;1089:454–61.
Lalli MA, Bettcher BM, Arcila ML, Garcia G, Guzman C, Madrigal L, et al. Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer’s disease. Mol Psychiatry. 2015;20:1294–300.
Xu M, Zhang DF, Luo R, Wu Y, Zhou H, Kong LL, et al. A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer’s disease. Alzheimers Dement. 2018;14:215–29.
Sood S, Gallagher IJ, Lunnon K, Rullman E, Keohane A, Crossland H, et al. A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status. Genome Biol. 2015;16:185.
Matarin M, Salih DA, Yasvoina M, Cummings DM, Guelfi S, Liu W, et al. A genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology. Cell Rep. 2015;10:633–44.
Bis JC, Jian X, Kunkle BW, Chen Y, Hamilton-Nelson KL, Bush WS, et al. Whole exome sequencing study identifies novel rare and common Alzheimer’s-associated variants involved in immune response and transcriptional regulation. Mol Psychiatry. 2020;25:1859–75.
Bhattacharya S, Dunn P, Thomas CG, Smith B, Schaefer H, Chen J, et al. ImmPort, toward repurposing of open access immunological assay data for translational and clinical research. Sci Data. 2018;5:180015.
Bi R, Zhang W, Zhang DF, Xu M, Fan Y, Hu QX, et al. Genetic association of the cytochrome c oxidase-related genes with Alzheimer’s disease in Han Chinese. Neuropsychopharmacology. 2018;43:2264–76.
Zhang DF, Li J, Wu H, Cui Y, Bi R, Zhou HJ, et al. CFH variants affect structural and functional brain changes and genetic risk of Alzheimer’s disease. Neuropsychopharmacology. 2016;41:1034–45.
Li GD, Bi R, Zhang DF, Xu M, Luo R, Wang D, et al. Female-specific effect of the BDNF gene on Alzheimer’s disease. Neurobiol Aging. 2017;53(192):e11–9.
Wang HZ, Bi R, Hu QX, Xiang Q, Zhang C, Zhang DF, et al. Validating GWAS-identified risk loci for Alzheimer’s disease in Han Chinese populations. Mol Neurobiol. 2016;53:379–90.
Cao Y, Li L, Xu M, Feng Z, Sun X, Lu J, et al. The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals. Cell Res. 2020;30:717–31.
Wang D, Fan Y, Malhi M, Bi R, Wu Y, Xu M, et al. Missense variants in HIF1A and LACC1 contribute to leprosy risk in Han Chinese. Am J Hum Genet. 2018;102:794–805.
Li X, Xu M, Bi R, Tan LW, Yao YG, Zhang DF. Common and rare variants of EGF increase the genetic risk of Alzheimer’s disease as revealed by targeted sequencing of growth factors in Han Chinese. Neurobiol Aging. 2022;S0197-4580(22)00223-8.
Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30:2114–20.
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60.
McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20:1297–303.
Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 2010;38:e164.
Jagadeesh KA, Wenger AM, Berger MJ, Guturu H, Stenson PD, Cooper DN, et al. M-CAP eliminates a majority of variants of uncertain significance in clinical exomes at high sensitivity. Nat Genet. 2016;48:1581–6.
Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.
Sun BB, Maranville JC, Peters JE, Stacey D, Staley JR, Blackshaw J, et al. Genomic atlas of the human plasma proteome. Nature. 2018;558:73–9.
Folkersen L, Fauman E, Sabater-Lleal M, Strawbridge RJ, Franberg M, Sennblad B, et al. Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease. PLoS Genet. 2017;13:e1006706.
Gauderman WJ. Sample size requirements for matched case-control studies of gene-environment interaction. Stat Med. 2002;21:35–50.
Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36:1–48.
Lee S, Emond MJ, Bamshad MJ, Barnes KC, Rieder MJ, Nickerson DA, et al. Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies. Am J Hum Genet. 2012;91:224–37.
Zuena AR, Casolini P, Lattanzi R, Maftei D. Chemokines in Alzheimer’s disease: new insights into prokineticins, chemokine-like proteins. Front Pharmacol. 2019;10:622.
Pellicano M, Bulati M, Buffa S, Barbagallo M, Di Prima A, Misiano G, et al. Systemic immune responses in Alzheimer’s disease: in vitro mononuclear cell activation and cytokine production. J Alzheimers Dis. 2010;21:181–92.
Reale M, Iarlori C, Feliciani C, Gambi D. Peripheral chemokine receptors, their ligands, cytokines and Alzheimer’s disease. J Alzheimers Dis. 2008;14:147–59.
Lee JK, Schuchman EH, Jin HK, Bae JS. Soluble CCL5 derived from bone marrow-derived mesenchymal stem cells and activated by amyloid beta ameliorates Alzheimer’s disease in mice by recruiting bone marrow-induced microglia immune responses. Stem Cells. 2012;30:1544–55.
Piehl N, van Olst L, Ramakrishnan A, Teregulova V, Simonton B, Zhang Z, et al. Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment. Cell. 2022. https://doi.org/10.1016/j.cell.2022.11.019.
Yeung SS, Ho YS, Chang RC. The role of meningeal populations of type II innate lymphoid cells in modulating neuroinflammation in neurodegenerative diseases. Exp Mol Med. 2021;53:1251–67.
Chen ZY, Zhang Y. Animal models of Alzheimer’s disease: Applications, evaluation, and perspectives. Zool Res. 2022;43:1026–40.