Immune response and endocytosis pathways are associated with the resilience against Alzheimer’s disease
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Abstract
Developing Alzheimer’s disease (AD) is influenced by multiple genetic variants that are involved in five major AD-pathways. Per individual, these pathways may differentially contribute to the modification of the AD-risk. The pathways involved in the resilience against AD have thus far been poorly addressed. Here, we investigated to what extent each molecular mechanism associates with (i) the increased risk of AD and (ii) the resilience against AD until extreme old age, by comparing pathway-specific polygenic risk scores (pathway-PRS). We used 29 genetic variants associated with AD to develop pathway-PRS for five major pathways involved in AD. We developed an integrative framework that allows multiple genes to associate with a variant, and multiple pathways to associate with a gene. We studied pathway-PRS in the Amsterdam Dementia Cohort of well-phenotyped AD patients ( N = 1895), Dutch population controls from the Longitudinal Aging Study Amsterdam ( N = 1654) and our unique 100-plus Study cohort of cognitively healthy centenarians who avoided AD ( N = 293). Last, we estimated the contribution of each pathway to the genetic risk of AD in the general population. All pathway-PRS significantly associated with increased AD-risk and (in the opposite direction) with resilience against AD (except for angiogenesis , p < 0.05). The pathway that contributed most to the overall modulation of AD-risk was β-amyloid metabolism (29.6%), which was driven mainly by APOE -variants. After excluding APOE variants, all pathway-PRS associated with increased AD-risk (except for angiogenesis, p < 0.05), while specifically immune response ( p = 0.003) and endocytosis ( p = 0.0003) associated with resilience against AD. Indeed, the variants in these latter two pathways became the main contributors to the overall modulation of genetic risk of AD (45.5% and 19.2%, respectively). The genetic variants associated with the resilience against AD indicate which pathways are involved with maintained cognitive functioning until extreme ages. Our work suggests that a favorable immune response and a maintained endocytosis pathway might be involved in general neuro-protection, which highlight the need to investigate these pathways, next to β-amyloid metabolism.
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Phagocytosis and endocytosis might underlie synaptic resilience in AsymAD individuals.
“previous evidence suggest that phagocytosis and endocytosis might underlie synaptic resilience in AsymAD individuals [92, 98].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [92]
The Discussion links immune response and endocytosis to escaping AD and suggests that dysregulation of these pathways may favor synapse engulfment. But the study examines cognitively healthy centenarians, not AsymAD individuals, and does not establish phagocytosis and endocytosis as mechanisms of synaptic resilience in that group. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGenetic variants of genes related to autophagy functions are involved in resilience against AD neuropathology.
“However, it has been reported that genetic variants of genes related to autophagy functions are involved in resilience against AD neuropathology [82, 92, 107].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [92]
The Discussion (page unavailable) associates genetic variants in immune-response and endocytosis pathways with resilience against AD in cognitively healthy centenarians. Autophagy was not among the five pathways studied, and resilience was assessed through avoidance of AD rather than resistance to measured AD neuropathology. Those specific parts of the claim are not supported by this paper. (LLM, conf=0.84)
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Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247 · see citing works
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108 · see citing works
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336 · see citing works
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · see citing works
Next-generation genotype imputation service and methods
Das, S., Forer, L., Schönherr, S., Sidore, C., Locke, A. E., Kwong, A., Vrieze, S. I., Chew, E. Y., Levy, S., McGue, M., et al. (2016) · Nature Genetics · doi:10.1038/ng.3656 · Cited by 4,190 · see citing works
Functional mapping and annotation of genetic associations with FUMA
Watanabe, K., Taskesen, E., van Bochoven, A., & Posthuma, D. (2017) · Nature Communications · doi:10.1038/s41467-017-01261-5 · Cited by 4,083 · see citing works
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Alzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946 · see citing works
A reference panel of 64,976 haplotypes for genotype imputation
the Haplotype Reference Consortium (2016) · Nature Genetics · doi:10.1038/ng.3643 · Cited by 2,836 · see citing works
Variant of <i>TREM2</i> Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558 · see citing works
Jansen, I. E., Savage, J. E., Watanabe, K., Bryois, J., Williams, D. M., Steinberg, S., Sealock, J., Karlsson, I. K., Hägg, S., Athanasiu, L., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0311-9 · Cited by 2,277 · see citing works
Self-citationGenome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234 · see citing works
Initiative, T. A. D. N., Hollingworth, P., CHARGE consortium, EADI1 consortium, Harold, D., Sims, R., Gerrish, A., Lambert, J.-C., Carrasquillo, M. M., Abraham, R., et al. (2011) · Nature Genetics · doi:10.1038/ng.803 · Cited by 1,997 · see citing works
How neuroinflammation contributes to neurodegeneration
Ransohoff, R. M. (2016) · Science · doi:10.1126/science.aag2590 · Cited by 1,967 · cited 1× · see citing works
“13 consequence of β-amyloid metabolism.[58, 59] In addition, previous studies showed that healthy immune and 359 metabolic systems are associated with longer and healthier lifespan.”
ResultMicroglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935 · see citing works
Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease
Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Rimmler, J. B., Locke, P. A., Conneally, P. M., Schmader, K. E., et al. (1994) · Nature Genetics · doi:10.1038/ng0694-180 · Cited by 1,920 · see citing works
Naj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · see citing works
Expansion of the Gene Ontology knowledgebase and resources
The Gene Ontology Consortium (2017) · Nucleic Acids Research · doi:10.1093/nar/gkw1108 · Cited by 1,850 · see citing works
Ageing as a Risk Factor for Disease
Niccoli, T., & Partridge, L. (2012) · Current Biology · doi:10.1016/j.cub.2012.07.024 · Cited by 1,831 · see citing works
Power and predictive accuracy of polygenic risk scores
Dudbridge, F. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003348 · Cited by 1,509 · cited 2× · see citing works
“[28, 29] In a typical polygenic risk 71 score, the effect-sizes of all genetic variants that significantly associate with a trait are combined.[30] In a pathway72 specific PRS, additional information is necessary: (i) the association of genetic variants to genes, and (ii) the association 73 of genes to pathways.”
BackgroundMethodFacing up to the global challenges of ageing
Partridge, L., Deelen, J., & Slagboom, P. E. (2018) · Nature · doi:10.1038/s41586-018-0457-8 · Cited by 1,475 · see citing works
Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
Seshadri, S. (2010) · JAMA · doi:10.1001/jama.2010.574 · Cited by 1,219 · see citing works
ARUK Consortium, Sims, R., GERAD/PERADES, C., van der Lee, S. J., Naj, A. C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., Kunkle, B. W., Boland, A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3916 · Cited by 1,126 · see citing works
2012 Alzheimer's disease facts and figures Alzheimer's Association ∗
Thies, W. H., & Bleiler, L. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.02.001 · Cited by 984 · see citing works
The genetic landscape of Alzheimer disease: clinical implications and perspectives
Van Cauwenberghe, C., Van Broeckhoven, C., & Sleegers, K. (2016) · Genetics in Medicine · doi:10.1038/gim.2015.117 · Cited by 863 · see citing works
TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
Wang, Y., Ulland, T. K., Ulrich, J. D., Song, W., Tzaferis, J. A., Hole, J. T., Yuan, P., Mahan, T. E., Shi, Y., Gilfillan, S., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151948 · Cited by 840 · see citing works
Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Michelle Luciano, A., Hill, W. D., Hagenaars, S. P., Ritchie, S. J., Marioni, R. E., Fawns‐Ritchie, C., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04362-x · Cited by 668 · see citing works
GWAS on family history of Alzheimer’s disease
Marioni, R. E., Harris, S. E., Zhang, Q., McRae, A. F., Hagenaars, S. P., Hill, W. D., Davies, G., Ritchie, C. W., Gale, C. R., Starr, J. M., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0150-6 · Cited by 564 · see citing works
Dementia incidence continues to increase with age in the oldest old: The 90+ study
Corrada, M. M., Brookmeyer, R., Paganini‐Hill, A., Berlau, D., & Kawas, C. H. (2010) · Annals of Neurology · doi:10.1002/ana.21915 · Cited by 523 · see citing works
Cohort Profile: The Longitudinal Aging Study Amsterdam
Huisman, M. A., Poppelaars, J. L., van der Horst, M., Beekman, A. T. F., Brug, J., van Tilburg, T. G., & Deeg, D. J. H. (2011) · International Journal of Epidemiology · doi:10.1093/ije/dyq219 · Cited by 467 · see citing works
Self-citationIsolation of glia from Alzheimer’s mice reveals inflammation and dysfunction
Orre, M., Kamphuis, W., Osborn, L. M., Jansen, A. H. P., Kooijman, L., Bossers, K., & Hol, E. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.06.004 · Cited by 394 · see citing works
Optimizing Patient Care and Research: The Amsterdam Dementia Cohort
van der Flier, W. M., Pijnenburg, Y. A. L., Prins, N. D., Lemstra, A. W., Bouwman, F. H., Teunissen, C. E., van Berckel, B. N. M., Stam, C. J., Barkhof, F., Visser, P. J., et al. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132306 · Cited by 390 · see citing works
Self-citationGenetics of healthy aging and longevity
Brooks-Wilson, A. R. (2013) · Human Genetics · doi:10.1007/s00439-013-1342-z · Cited by 380 · see citing works
Amsterdam Dementia Cohort: Performing Research to Optimize Care
van der Flier, W. M., & Scheltens, P. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170850 · Cited by 379 · see citing works
Self-citationUntangling the brain’s neuroinflammatory and neurodegenerative transcriptional responses
Srinivasan, K., Friedman, B. A., Larson, J. L., Lauffer, B. E., Goldstein, L. D., Appling, L. L., Borneo, J., Poon, C., Ho, T., Cai, F., et al. (2016) · Nature Communications · doi:10.1038/ncomms11295 · Cited by 336 · see citing works
Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease
DemGene, Steinberg, S., Stefansson, H., Jonsson, T., Johannsdottir, H., Ingason, A., Helgason, H., Sulem, P., Magnusson, O. T., Gudjonsson, S. A., et al. (2015) · Nature Genetics · doi:10.1038/ng.3246 · Cited by 324 · see citing works
Bennett, R. E., Robbins, A. B., Hu, M., Cao, X., Betensky, R. A., Clark, T., Das, S., & Hyman, B. T. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710329115 · Cited by 299 · see citing works
A novel Alzheimer disease locus located near the gene encoding tau protein
Jun, G., Ibrahim-Verbaas, C. A., Vronskaya, M., Lambert, J.-C., Chung, J., Naj, A. C., Kunkle, B. W., Wang, L.-S., Bis, J. C., Bellenguez, C., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.23 · Cited by 297 · see citing works
van der Lee, S. J., Wolters, F. J., Ikram, M. K., Albert Hofman, D., Ikram, M. A., Amin, N., & van Duijn, C. M. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30053-x · Cited by 297 · see citing works
Timmers, P. R. H. J., Mounier, N., Läll, K., Fischer, K., Zheng, N., Feng, X., Bretherick, A. D., Clark, D. W., Agbessi, M. D. T., Ahsan, H., et al. (2019) · eLife · doi:10.7554/elife.39856 · Cited by 277 · see citing works
Alzheimer's disease and angiogenesis
Vagnucci, A. H., & Li, W. W. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12521-4 · Cited by 267 · see citing works
Marco, L. Y. D., Venneri, A., Farkas, E., Evans, P. C., Marzo, A., & Frangi, A. F. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.08.014 · Cited by 258 · see citing works
The Longitudinal Aging Study Amsterdam: cohort update 2016 and major findings
Hoogendijk, E. O., Deeg, D. J. H., Poppelaars, J. L., van der Horst, M. H. L., Groenou, M. I. B. V., Comijs, H. C., Pasman, H. R. W., van Schoor, N. M., Suanet, B., Thomése, F., et al. (2016) · European Journal of Epidemiology · doi:10.1007/s10654-016-0192-0 · Cited by 227 · see citing works
Self-citationAlzheimer's disease and angiogenesis
Agorogiannis, E. I., & Agorogiannis, G. I. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13000-0 · Cited by 224 · see citing works
Understanding Alzheimer Disease at the Interface between Genetics and Transcriptomics
Verheijen, J., & Sleegers, K. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.02.007 · Cited by 189 · see citing works
Polygenic score prediction captures nearly all common genetic risk for Alzheimer's disease
Escott-Price, V., Shoai, M., Pither, R., Williams, J., & Hardy, J. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.018 · Cited by 183 · see citing works
Genomic variants, genes, and pathways of Alzheimer's disease: An overview
Naj, A. C., & Schellenberg, G. D. (2016) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32499 · Cited by 178 · see citing works
Polygenic risk score analysis of pathologically confirmed Alzheimer disease
Escott‐Price, V., Myers, A., Huentelman, M. J., & Hardy, J. (2017) · Annals of Neurology · doi:10.1002/ana.24999 · Cited by 178 · see citing works
Pathways to Alzheimer's disease
Hardy, J., Bogdanović, N., Winblad, B. G., Portelius, E., Andreasen, N. C., Cedazo-Mı́nguez, Á., & Zetterberg, H. (2014) · Journal of Internal Medicine · doi:10.1111/joim.12192 · Cited by 177 · see citing works
Joshi, P. K., Pirastu, N., Kentistou, K. A., Fischer, K., Hofer, E., Schraut, K. E., Clark, D. W., Nutile, T., Barnes, C. L. K., Timmers, P. R. H. J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00934-5 · Cited by 161 · see citing works
Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease
Desikan, R. S., Schork, A. J., Wang, Y., Thompson, W. K., Dehghan, A., Ridker, P. M., Chasman, D. I., McEvoy, L. K., Holland, D., Chen, C.-H., et al. (2015) · Circulation · doi:10.1161/circulationaha.115.015489 · Cited by 135 · see citing works
Darst, B. F., Koscik, R. L., Racine, A. M., Oh, J. M., Krause, R. A., Carlsson, C. M., Zetterberg, H., Blennow, K., Christian, B. T., Bendlin, B. B., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160195 · Cited by 129 · see citing works
DESGESCO (Dementia Genetics Spanish Consortium), E. (. D. E. D. B., van der Lee, S. J., biobank), E. (. D. E. D., IFGC (International FTD-Genomics Consortium), I. (. I. P. D. G. C., IPDGC (The International Parkinson Disease Genomics Consortium), Dementia), R.-F. (. A. M. F. I. F.-T., (NBB), N. B. B., The GIFT (Genetic Investigation in Frontotemporal Dementia and Alzheimer’s Disease) Study Group, Conway, O. J., Jansen, I., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02026-8 · Cited by 120 · see citing works
Self-citationGenetic risk for alzheimer disease is distinct from genetic risk for amyloid deposition
Leonenko, G., Shoai, M., Bellou, E., Sims, R., Williams, J., Hardy, J., Escott‐Price, V., & Initiative, T. A. D. N. (2019) · Annals of Neurology · doi:10.1002/ana.25530 · Cited by 114 · see citing works
Evaluation of a Genetic Risk Score to Improve Risk Prediction for Alzheimer’s Disease
Chouraki, V., for the International Genomics of Alzheimer’s Project, Reitz, C., Maury, F., Bis, J. C., Bellenguez, C., Yu, L., Jakobsdottir, J., Mukherjee, S., Adams, H. H., et al. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-150749 · Cited by 98 · see citing works
Alzheimer’s disease polygenic risk score as a predictor of conversion from mild-cognitive impairment
Chaudhury, S. R., Brookes, K. J., Patel, T., Fallows, A., Guetta‐Baranes, T., Turton, J. C., Guerreiro, R. J., Brás, J., Hardy, J., Francis, P. T., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0485-7 · Cited by 89 · see citing works
The 100-plus Study of cognitively healthy centenarians: rationale, design and cohort description
Holstege, H., Beker, N., Dijkstra, T., Pieterse, K., Wemmenhove, E., Schouten, K., Thiessens, L., Horsten, D., Rechtuijt, S., Sikkes, S., et al. (2018) · bioRxiv · doi:10.1007/s10654-018-0451-3 · Cited by 86 · see citing works
Self-citationAdjusting the compass: new insights into the role of angiogenesis in Alzheimer’s disease
Jefferies, W. A., Price, K. A., Biron, K. E., Fenninger, F., Pfeifer, C. G., & Dickstein, D. L. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt230 · Cited by 85 · see citing works
The Role of Genetics in Advancing Precision Medicine for Alzheimer’s Disease—A Narrative Review
Freudenberg‐Hua, Y., Li, W., & Davies, P. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00108 · Cited by 74 · see citing works
Tesi, N., van der Lee, S. J., Hulsman, M., Jansen, I. E., Stringa, N., van Schoor, N., Meijers-Heijboer, H., Huisman, M., Scheltens, P., Reinders, M. J. T., et al. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-018-0273-5 · Cited by 65 · see citing works
Self-citationAhmad, S., Bannister, C. A., van der Lee, S. J., Vojinović, D., Adams, H. H. H., Ramı́rez, A., Escott‐Price, V., Sims, R., Baker, E. A., Williams, J. H., et al. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.01.005 · Cited by 44 · see citing works
The Netherlands Brain Bank for Psychiatry
(2018) · Handbook of Clinical Neurology · doi:10.1016/b978-0-444-63639-3.00001-3 · Cited by 22 · see citing works
Chaudhury, S. R., Brookes, K. J., Patel, T., Fallows, A., Guetta‐Baranes, T., Turton, J. C., Guerreiro, R. J., Brás, J., Hardy, J., Francis, P. T., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0503-9 · Cited by 7 · see citing works
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van Bokhoven, P., de Wilde, A., Vermunt, L., Leferink, P. S., Heetveld, S., Cummings, J., Scheltens, P., & Vijverberg, E. G. B. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00927-z · Cited by 123 · see citing works
Self-citationWestern, D., Timsina, J., Wang, L., Wang, C., Yang, C., Phillips, B., Wang, Y., Liu, M., Ali, M., Beric, A., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01972-8 · Cited by 111 · see citing works
Mukhopadhyay, S., & Banerjee, D. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215065 · Cited by 66 · see citing works
snpXplorer: a web application to explore human SNP-associations and annotate SNP-sets
Tesi, N., van der Lee, S. J., Hulsman, M., Holstege, H. H., & Reinders, M. J. T. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab410 · Cited by 49 · see citing works
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Baker, E. A., Leonenko, G., Schmidt, K. M., Hill, M., Myers, A., Shoai, M., de Rojas, I., Tesi, N., Holstege, H. H., van der Flier, W. M., et al. (2023) · PLoS ONE · doi:10.1371/journal.pone.0281440 · Cited by 50 · see citing works
Self-citationYang, H., Teng, L., Kang, D., Menon, V., Ge, T., Finucane, H. K., Schultz, A. P., Properzi, M. J., Klein, H., Chibnik, L. B., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43132-2 · Cited by 51 · see citing works
Zhang, M., Ganz, A. B., Rohde, S., Rozemuller, A. J. M., Bank, N. B., Reinders, M. J. T., Scheltens, P., Hulsman, M., Hoozemans, J. J. M., & Holstege, H. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12899 · Cited by 43 · see citing works
Self-citationPolygenic Risk Score of Longevity Predicts Longer Survival Across an Age Continuum
Tesi, N., van der Lee, S. J., Hulsman, M., Jansen, I. E., Stringa, N., van Schoor, N. M., Scheltens, P., van der Flier, W. M., Huisman, M. A., Reinders, M. J. T., et al. (2020) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaa289 · Cited by 37 · see citing works
Self-citationGlymphatic system clearance and Alzheimer’s disease risk: a CSF proteome-wide study
Cullell, N., Caruana, G., Elias-Mas, A., Delgado-Sánchez, A., Artero, C., Buongiorno, M., Almería, M., Ray, N. J., Corrêa, S. A. L., & Krupiński, J. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01612-7 · Cited by 29 · see citing works
Galvin, J. E., Kleiman, M. J., Chrisphonte, S., Cohen, I., Disla, S., Galvin, C. B., Greenfield, K. K., Moore, C., Rawn, S., Riccio, M. L., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215077 · Cited by 29 · see citing works
Jaye, S., Sandau, U. S., & Saugstad, J. A. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1378576 · Cited by 26 · see citing works
Immune dysfunction in Alzheimer disease
Butovsky, O., Rosenzweig, N., Kleemann, K. L., Jorfi, M., Kuchroo, V. K., Tanzi, R. E., & Weiner, H. L. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00997-0 · Cited by 34 · see citing works
Pyun, J., Park, Y. H., Lee, K., Kim, S., Saykin, A. J., Nho, K. T., & Initiative, A. D. N. (2021) · Translational Neurodegeneration · doi:10.1186/s40035-021-00259-w · Cited by 25 · see citing works
Jury-Garfe, N., Redding-Ochoa, J., You, Y., Martínez, P., Karahan, H., Chimal-Juárez, E., Johnson, T. S., Zhang, J., Resnick, S., Kim, J., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02775-1 · Cited by 22 · see citing works
“Although our data support previous evidence suggesting that endocytosis and phagocytosis might underlie synaptic resilience in AsymAD individuals [27, 92], the literature also indicates the role of some of these DEGs in actin-based motility (pink highlighted genes in Fig.”
BackgroundResultAlzheimer’s disease is an inherent, natural part of human brain aging: an integrated perspective
Ferrer, I. (2022) · Free Neuropathology · doi:10.17879/freeneuropathology-2022-3806 · Cited by 21 · see citing works
Longevity, Centenarians and Modified Cellular Proteodynamics
Frankowska, N., Bryl, E., Fülöp, T., & Witkowski, J. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032888 · Cited by 19 · see citing works
Schork, N. J., Elman, J. A., & Initiative, A. D. N. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230548 · Cited by 20 · see citing works
Polygenic effects on the risk of Alzheimer’s disease in the Japanese population
Kikuchi, M., Miyashita, A., Hara, N., Kasuga, K., Saito, Y., Murayama, S., Kakita, A., Akatsu, H., Ozaki, K., Niida, S., et al. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01414-x · Cited by 19 · see citing works
Tomassen, J., den Braber, A., van der Landen, S. M., Konijnenberg, E., Teunissen, C. E., Vermunt, L., de Geus, E. J. C., Boomsma, D. I., Scheltens, P., Tijms, B. M., et al. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12346 · Cited by 16 · see citing works
Self-citationTomassen, J., den Braber, A., van der Lee, S. J., Reus, L. M., Konijnenberg, E., Carter, S. F., Yaqub, M. M., van Berckel, B. N. M., Collij, L. E., Boomsma, D. I., et al. (2022) · BMC Neurology · doi:10.1186/s12883-022-02925-6 · Cited by 18 · see citing works
Self-citationLorenzini, L., Collij, L. E., Tesi, N., Vilor‐Tejedor, N., Ingala, S., Blennow, K., Foley, C., Frisoni, G. B., Haller, S., Holstege, H. H., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14096 · Cited by 17 · see citing works
Self-citationXu, Y., Vasiljevic, E., Deming, Y. K., Jonaitis, E. M., Koscik, R. L., Hulle, C. A. V., Lu, Q., Carboni, M., Kollmorgen, G., Wild, N., et al. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230097 · Cited by 16 · see citing works
Molecular hallmarks of excitatory and inhibitory neuronal resilience to Alzheimer’s disease
Castanho, I., Yeganeh, P. N., Boix, C. A., Morgan, S. L., Mathys, H., Prokopenko, D., White, B., Soto, L. M., Pegoraro, G., Shah, S. A., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00892-3 · Cited by 22 · see citing works
Upadhya, S., Liu, H., Luo, S., Lutz, M. W., & Chiba‐Falek, O. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.827447 · Cited by 15 · see citing works
The unique neuropathological vulnerability of the human brain to aging
Ferrer, I. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101916 · Cited by 14 · see citing works
Zhang, C., Liu, Y., Zeng, L., Luo, X., Fan, G., Shi, H., & Shen, J. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.02.015 · Cited by 13 · see citing works
The Effect of Alzheimer’s Disease-Associated Genetic Variants on Longevity
Tesi, N., Hulsman, M., van der Lee, S. J., Jansen, I. E., Stringa, N., van Schoor, N. M., Scheltens, P., van der Flier, W. M., Huisman, M. A., Reinders, M. J. T., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.748781 · Cited by 13 · see citing works
Self-citationGenetic trade‐offs between complex diseases and longevity
Hu, D., Li, Y., Zhang, D., Ding, J., Song, Z., Min, J., Zeng, Y., & Nie, C. (2022) · Aging Cell · doi:10.1111/acel.13654 · Cited by 11 · see citing works
Lu, A., Chen, W.-T., Dalby, M., García, D. S., Vanheusden, M., de Vries, L. E., van Lieshout, V., Martirosyan, A., Craessaerts, K., Moonen, S., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04393-8 · Cited by 13 · see citing works
Self-citationHermansen, M., Nygaard, M., Tan, Q., Jeune, B., Semkovska, M., Christensen, K., Thinggaard, M., & Mengel‐From, J. (2024) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2024.105398 · Cited by 12 · see citing works
Upregulation of endocytic protein expression in the Alzheimer’s disease male human brain
Alsaqati, M., Thomas, R. S., & Kidd, E. J. (2023) · Aging Brain · doi:10.1016/j.nbas.2023.100084 · Cited by 10 · see citing works
Research Progress of Targeting Neuro-Immune Inflammation in the Treatment of Alzheimer's Disease
Chen, H., Deng, C., Meng, Z., & Meng, S. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2711312 · Cited by 10 · see citing works
Improving the Utility of Polygenic Risk Scores as a Biomarker for Alzheimer’s Disease
Vlachakis, D., Papakonstantinou, E., Sagar, R., Bacopoulou, F., Exarchos, T. P., Kourouthanassis, P. E., Karyotis, V. A., Vlamos, P., Lyketsos, C. G., Avramopoulos, D., et al. (2021) · Cells · doi:10.3390/cells10071627 · Cited by 10 · see citing works
Revolutionizing Alzheimer’s Detection: Immune-Related Gene Biomarkers as Non-Invasive Predictors
Abed, S., Ebrahimi, A., Fattahi, F., Khaniani, M. S., & Derakhshan, S. M. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04970-x · Cited by 8 · see citing works
Gómez, G., Shi, L., Fohner, A. E., Chen, J., Yang, Y., Fornage, M., Duggan, M. R., Peng, Z., Daya, G. N., Tin, A., et al. (2024) · medRxiv · doi:10.1101/2024.10.07.24314972 · Cited by 7 · see citing works
Effect of Proinflammatory S100A9 Protein on Migration and Proliferation of Microglial Cells
Bai, Q., Sun, D., Zeng, Y., Zhu, J., Zhang, C., Zhang, X., Chen, L., Zhou, X., Ye, L., Tang, Y. C., et al. (2023) · Journal of Molecular Neuroscience · doi:10.1007/s12031-023-02168-1 · Cited by 6 · see citing works
Resistance and Resilience to Alzheimer's DiseasePreprint
Latimer, C. S., Prater, K. E., Postupna, N. O., & Keene, C. D. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041201 · Cited by 5 · see citing works
Pathway‐based polygenic risk of Alzheimer's disease highlights immune genes in cognitive decline
Romic, E., Karlsson, I., Karalija, N., Adolfsson, A. N., Adolfsson, R., & Kauppi, K. (2026) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.70209 · Cited by 4 · see citing works
Connecting dementia risk loci to the CSF proteome identifies pathophysiological leads for dementia
Reus, L. M., Jansen, I. E., Tijms, B. M., Visser, P. J., Tesi, N., van der Lee, S. J., Vermunt, L., Peeters, C. F. W., Groot, L. A. D., Hok‐A‐Hin, Y. S., et al. (2024) · Brain · doi:10.1093/brain/awae090 · Cited by 5 · see citing works
Self-citationPérez-González, A. P., de Anda‐Jáuregui, G., & Lemus, E. H. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052361 · Cited by 4 · see citing works
Li, X., Fernandes, B. S., Liu, A., Chen, J., Chen, X., Zhao, Z., & Dai, Y. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70779 · Cited by 4 · see citing works
Castanho, I., Yeganeh, P. N., Boix, C. A., Morgan, S. L., Mathys, H., Prokopenko, D., White, B., Soto, L. M., Pegoraro, G., Shah, S. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.13.632801 · Cited by 4 · see citing works
Rose, S. E., Prater, K. E., Mamde, S., Smith, I., Lin, Y. F., Cochoit, A., Reid, A. N., Johnson, C. S. C., Qiu, W., Strohbehn, S. D., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.16.643481 · Cited by 4 · see citing works
Kumar, A., Binette, A. P., Bali, D., Janelidze, S., Stomrud, E., Palmqvist, S., Vogel, J. W., Hansson, O., & Mattsson, N. (2025) · Brain Communications · doi:10.1093/braincomms/fcaf353 · Cited by 3 · see citing works
Mustafa, Y., Main, L. R., Mews, M., Janve, V. A., Hohman, T. J., Haines, J. L., Song, Y. E., Griswold, A. J., Pericak‐Vance, M. A., Scott, W. K., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03698-5 · Cited by 3 · see citing works
Biomarkers, Cognitive Function, and Mortality in Centenarians
Shikimoto, R., Sasaki, T., Abe, Y., Tai, K., Hirose, N., Okano, H., & Arai, Y. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.11335 · Cited by 3 · see citing works
Jury, N., You, Y., Martínez, P., Redding‐Ochoa, J., Karahan, H., Johnson, T. S., Zhang, J., Kim, J., Troncoso, J. C., & Lasagna‐Reeves, C. A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.27.550884 · Cited by 3 · see citing works
Advances in Genetic Risk Scores for Alzheimer’s Disease and Dementia: A Systematic Review
Sampatakakis, S. N., Mourtzi, N., Hatzimanolis, A., & Scarmeas, N. (2025) · Neurology International · doi:10.3390/neurolint17070099 · Cited by 3 · see citing works
Pratt, T., Lee, A., Zheng, J., Tavacoli, F., Ho, H., Liu, T., Zhan, H., Chen, J., & Initiative, A. D. N. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251362258 · Cited by 2 · see citing works
Associating brain imaging phenotypes and genetic risk factors via a hypergraph based netNMF method
Zhuang, J., Tian, J., Xiong, X., Li, T., Chen, Z., Chen, R., Chen, J., & Li, X. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1052783 · Cited by 2 · see citing works
Luckett, E. S., Abakkouy, Y., Lorenzini, L., Collij, L. E., García, D. V., Visser, P. J., den Braber, A., Ritchie, C. W., Boada, M., Genius, P., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70376 · Cited by 1 · see citing works
Fitzsimons, L. A., Atif-Sheikh, M., Mueth, M. G., Rice, M., Howell, G. R., & Harrison, B. J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.24.604961 · Cited by 1 · see citing works
Kikuchi, M., Miyashita, A., Hirota, Y., Hara, N., Hasegawa, M., Sakakibara, Y., Sekiya, M., Ozaki, K., Niida, S., Morishima, M., et al. (2025) · medRxiv · doi:10.1101/2025.10.06.25336925 · Cited by 1 · see citing works
Polygenic Risk Score Effectively Predicts Risk of Depression Onset in Alzheimer’s DiseasePreprint
Upadhya, S., Liu, H., Luo, S., Lutz, M. W., & Chiba‐Falek, O. (2021) · Research Square · doi:10.21203/rs.3.rs-845772/v1
Rubinski, A., Frerich, S., Malik, R., Franzmeier, N., Ramı́rez, A., Dichgans, M., Ewers, M., & Initiative, A. D. N. (2021) · medRxiv · doi:10.1101/2021.11.02.21265788
Moore, A. K., & Ritchie, M. D. (2023) · medRxiv · doi:10.1101/2023.11.06.23297993
Arai, Y., Shikimoto, R., Sasaki, T., Abe, Y., Tai, K., Hirose, N., & Okano, H. (2025) · Research Square · doi:10.21203/rs.3.rs-6808383/v1
Systems Immunology and Omics Data from Developing Countries Are Needed to Inform Vaccine Development
Mussá, T. (2025) · Springer eBooks · doi:10.1007/978-3-031-94540-3_12
Pyun, J.-M., Park, Y. H., Lee, K., Kim, S., Saykin, A. J., & Nho, K. T. (2021) · Figshare · doi:10.6084/m9.figshare.16551322
Tomassen, J., den Braber, A., van der Lee, S. J., Reus, L. M., Konijnenberg, E., Carter, S. F., Yaqub, M. M., van Berckel, B. N. M., Collij, L. E., Boomsma, D. I., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26554649
Self-citationTomassen, J., den Braber, A., van der Lee, S. J., Reus, L. M., Konijnenberg, E., Carter, S. F., Yaqub, M. M., van Berckel, B. N. M., Collij, L. E., Boomsma, D. I., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26554646
Self-citationTomassen, J., den Braber, A., van der Lee, S. J., Reus, L. M., Konijnenberg, E., Carter, S. F., Yaqub, M. M., van Berckel, B. N. M., Collij, L. E., Boomsma, D. I., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26554652
Self-citationAdditional file 2 of Polygenic effects on the risk of Alzheimer’s disease in the Japanese population
Kikuchi, M., Miyashita, A., Hara, N., Kasuga, K., Saito, Y., Murayama, S., Kakita, A., Akatsu, H., Ozaki, K., Niida, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25303168
Additional file 1 of Polygenic effects on the risk of Alzheimer’s disease in the Japanese population
Kikuchi, M., Miyashita, A., Hara, N., Kasuga, K., Saito, Y., Murayama, S., Kakita, A., Akatsu, H., Ozaki, K., Niida, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25302843
Genotype–phenotype interaction in Alzheimer's disease immune activation
Knudtzon, S. L., Kirsebom, B., Pålhaugen, L., Bettella, F., Gísladóttir, B., Bahrami, S., Athanasiu, L., Rongve, A., Nakling, A. E., Almdahl, I. S., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.70978
Bazemore, K., Iqbal, T., Kuzma, A. B., Grant, S. F. A., Schellenberg, G. D., Wang, L., Chesi, A., Jin, J., & Naj, A. C. (2026) · medRxiv · doi:10.64898/2026.05.25.26353905
Peripheral T-cell co-signalling states mark vulnerability and resilience to cerebral Aβ pathologyPreprint
Mallone, A., Bachmann, D., Rickenbach, C., Krueger, M., Kirabali, T., Zetterberg, H., Ferretti, M. T., Kulic, L., Höck, C., Nitsch, R. M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.03.742616
Valentim, C., Denecke, J., Frerich, S., Betthauser, T. J., Li, Y., Ahmadi, R., Franzmeier, N., (ADNI), A. D. N. I., Malik, R., & Ewers, M. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71939
- Authors
- Tesi, N., van der Lee, S. J., Hulsman, M., Jansen, I. E., Stringa, N., van Schoor, N. M., Scheltens, P., van der Flier, W. M., Huisman, M., Reinders, M. J. T., & Holstege, H.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Amsterdam Neuroscience (NL)
- Amsterdam Public Health (NL)
- Delft University of Technology (NL)
- Corresponding author
- Holstege, Henne
- ORCID
- Venue
- Translational Psychiatry
- Published
- 2020-09-29
- Volume
- 10
- Issue
- 1
- Pages
- 332-332
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC7524800
- OpenAlex
- W3090704421
- Cited by
- 67
- References
- 67
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 14 · 2023: 12 · 2022: 7 · 2021: 10 · 2020: 1
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- VU Research Portal (submittedVersion, other-oa)
- Research Repository (Delft University of Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- ZonMw (733051061, 733050814)
- Stichting Dioraphte
- Alzheimer Nederland (WE09.2014–03)
- Amsterdam Neuroscience
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, polygenic risk score, immune response, endocytosis, angiogenesis, centenarians, cognitive aging, neuroprotection
- MeSH terms
- Aged, 80 and over, Aging, Alzheimer Disease, Cognition, Endocytosis, Humans, Immunity
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