Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer’s pathology
Open accessAbstract
Conventional genetic approaches and computational strategies have converged on immune-inflammatory pathways as key events in the pathogenesis of late onset sporadic Alzheimer’s disease (LOAD). Mutations and/or differential expression of microglial specific receptors such as TREM2, CD33, and CR3 have been associated with strong increased risk for developing Alzheimer’s disease (AD). DAP12 (DNAX-activating protein 12)/TYROBP, a molecule localized to microglia, is a direct partner/adapter for TREM2, CD33, and CR3. We and others have previously shown that TYROBP expression is increased in AD patients and in mouse models. Moreover, missense mutations in the coding region of TYROBP have recently been identified in some AD patients. These lines of evidence, along with computational analysis of LOAD brain gene expression, point to DAP12/TYROBP as a potential hub or driver protein in the pathogenesis of AD. Using a comprehensive panel of biochemical, physiological, behavioral, and transcriptomic assays, we evaluated in a mouse model the role of TYROBP in early stage AD. We crossed an Alzheimer’s model mutant APP KM670/671NL /PSEN1 Δexon9 (APP/PSEN1) mouse model with Tyrobp −/− mice to generate AD model mice deficient or null for TYROBP (APP/PSEN1; Tyrobp +/− or APP/PSEN1; Tyrobp −/−). While we observed relatively minor effects of TYROBP deficiency on steady-state levels of amyloid-β peptides, there was an effect of Tyrobp deficiency on the morphology of amyloid deposits resembling that reported by others for Trem2 −/− mice. We identified modulatory effects of TYROBP deficiency on the level of phosphorylation of TAU that was accompanied by a reduction in the severity of neuritic dystrophy. TYROBP deficiency also altered the expression of several AD related genes, including Cd33. Electrophysiological abnormalities and learning behavior deficits associated with APP/PSEN1 transgenes were greatly attenuated on a Tyrobp-null background. Some modulatory effects of TYROBP on Alzheimer’s-related genes were only apparent on a background of mice with cerebral amyloidosis due to overexpression of mutant APP/PSEN1. These results suggest that reduction of TYROBP gene expression and/or protein levels could represent an immune-inflammatory therapeutic opportunity for modulating early stage LOAD, potentially leading to slowing or arresting the progression to full-blown clinical and pathological LOAD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Numerous studies targeting members of the TREM2/TYROBP pathway (Trem2, Tyrobp, and miR155) support beneficial outcomes associated with maintenance and/or restoration of homeostatic functions of microglia.
“Support for beneficial outcomes associated with maintenance and/or restoration of homeostatic functions of microglia comes from the numerous studies targeting the members of this pathway, including Trem2,48,50–52 Tyrobp,53,54 and miR155.41,55”
From Microglial <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [53]
The Discussion (page unavailable) reports that TYROBP deficiency in an early Alzheimer’s mouse model improved learning behavior and normalized some synaptic dysfunction, supporting a beneficial outcome from targeting Tyrobp. It does not establish that the benefit resulted from maintaining or restoring homeostatic microglial functions. (LLM, conf=0.83)
Experimental — accuracy not yet measuredManipulation of molecules involved in immune/microglial function in either direction may result in detrimental or exacerbated pathological outcomes.
“However, as we have previously seen in our studies modulating Tyrobp expression, manipulation of molecules involved in immune/microglial function in either direction may result in detrimental or exacerbated pathological outcomes.49,53,54,56”
From Microglial <i>INPP5D</i> limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [53]
The Discussion (page unavailable) says reduced TREM2 may be beneficial early but detrimental later, supporting the possibility that an immune-related manipulation can have harmful effects under some conditions. However, this paper found TYROBP deficiency protective in its early Alzheimer’s mouse model and says TYROBP overexpression was beyond its scope. It therefore does not establish detrimental outcomes from manipulating TYROBP in either direction. (LLM, conf=0.82)
Experimental — accuracy not yet measuredA reduction of Tyrobp has neuroprotective effects on AD pathology.
“Previous studies have shown that a reduction of Tyrobp has neuroprotective effects on AD pathology38,39.”
From Effects of SPI1-mediated transcriptome remodeling on Alzheimer's disease-related phenotypes in mouse models of Aβ amyloidosis (2024) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,706 · see citing works
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458 · 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
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
Lamb, J., Crawford, E. D., Peck, D., Modell, J. W., Blat, I. C., Wrobel, M. J., Lerner, J., Brunet, J.-P., Subramanian, A., Ross, K. N., et al. (2006) · Science · doi:10.1126/science.1132939 · Cited by 5,257 · 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
DrugBank: a comprehensive resource for in silico drug discovery and exploration
Wishart, D. S. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj067 · Cited by 3,892 · see citing works
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · cited 1× · see citing works
“When 5XFAD mice, which develop rapid and aggressive amyloid pathology and neuronal loss [56], were rendered deficient or null for TYROBP or TREM2, microglial clustering around plaques and plaque compaction were reduced at 4 months of age [85].”
BackgroundComplement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · 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
Relating protein pharmacology by ligand chemistry
Keiser, M. J., Roth, B. L., Armbruster, B. N., Ernsberger, P., Irwin, J. J., & Shoichet, B. K. (2007) · Nature Biotechnology · doi:10.1038/nbt1284 · Cited by 2,402 · see citing works
Memory deficits associated with senescence: A neurophysiological and behavioral study in the rat.
Barnes, C. A. (1979) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0077579 · Cited by 2,088 · 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
DrugBank 4.0: shedding new light on drug metabolism
Law, V., Knox, C., Djoumbou-Feunang, Y., Jewison, T., Guo, A. C., Liu, Y., Maciejewski, A., Arndt, D., Wilson, M., Neveu, V., et al. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1068 · Cited by 1,995 · 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
Predicting new molecular targets for known drugs
Keiser, M. J., Setola, V., Irwin, J. J., Laggner, C., Abbas, A. I., Hufeisen, S. J., Jensen, N. H., Kuijer, M. B., Matos, R. C., Tran, T. B., et al. (2009) · Nature · doi:10.1038/nature08506 · Cited by 1,667 · see citing works
Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
Zhang, B., Gaiteri, C., Bodea, L.-G., Wang, Z., McElwee, J., Podtelezhnikov, A. A., Zhang, C., Xie, T., Tran, L., Dobrin, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.030 · Cited by 1,657 · see citing works
Self-citationLi, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222 · see citing works
Oxidative stress and Alzheimer disease
Christen, Y. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.2.621s · Cited by 1,158 · see citing works
Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease
Outeiro, T. F., Kontopoulos, E., Altmann, S. M., Kufareva, I., Strathearn, K. E., Amore, A. M., Volk, C. B., Maxwell, M. M., Rochet, J., McLean, P. J., et al. (2007) · Science · doi:10.1126/science.1143780 · Cited by 1,066 · see citing works
Selective neuronal vulnerability to oxidative stress in the brain
Wang, X. (2010) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2010.00012 · Cited by 1,008 · see citing works
Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta
Griciuc, A., Serrano-Pozo, A., Parrado, A. R., Lesinski, A. N., Asselin, C. N., Mullin, K., Hooli, B., Choi, S. H., Hyman, B. T., & Tanzi, R. E. (2013) · Neuron · doi:10.1016/j.neuron.2013.04.014 · Cited by 1,004 · see citing works
Synaptic AMPA receptor plasticity and behavior
Kessels, H. W., & Malinow, R. (2009) · Neuron · doi:10.1016/j.neuron.2009.01.015 · Cited by 993 · 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
Co-expression of multiple transgenes in mouse CNS: a comparison of strategies
Jankowsky, J. L., Slunt, H. H., Ratovitski, T., Jenkins, N. A., Copeland, N. G., & Borchelt, D. (2001) · Biomolecular Engineering · doi:10.1016/s1389-0344(01)00067-3 · Cited by 819 · see citing works
Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.003 · Cited by 817 · see citing works
Discovery of drug mode of action and drug repositioning from transcriptional responses
Iorio, F., Bosotti, R., Scacheri, E., Belcastro, V., Mithbaokar, P., Ferriero, R., Murino, L., Tagliaferri, R., Brunetti-Pierri, N., Isacchi, A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000138107 · Cited by 816 · see citing works
Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses
Bertram, L., & Tanzi, R. E. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2494 · Cited by 747 · see citing works
Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello, C., Yuan, P., Schain, A., & Grutzendler, J. (2015) · Nature Communications · doi:10.1038/ncomms7176 · Cited by 718 · see citing works
Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20142322 · Cited by 682 · cited 11× · see citing works
“Thus, the effect of a decreased Tyrobp expression on the stoichiometry of TAU phosphorylation appeared to be different in the presence or absence of APP/PSEN1 mutations leading to amyloid deposition.”
BackgroundInfluentialCD33 Alzheimer's disease locus: altered monocyte function and amyloid biology
Initiative, T. A. D. N., Bradshaw, E. M., Chibnik, L. B., Keenan, B. T., Ottoboni, L., Raj, T., Tang, A., Rosenkrantz, L. L., Imboywa, S., Lee, M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3435 · Cited by 570 · see citing works
Bertram, L., Lange, C., Mullin, K., Parkinson, M., Hsiao, M., Hogan, M. F., Schjeide, B. M. M., Hooli, B., DiVito, J., Ionita, I., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.10.008 · Cited by 511 · see citing works
A neuromodulatory role of interleukin-1β in the hippocampus
Schneider, H., Pitossi, F., Balschun, D., Wagner, A., del Rey, A., & Besedovsky, H. O. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7778 · Cited by 498 · see citing works
Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts
Paloneva, J., Kestilä, M., Wu, J., Salminen, A., Böhling, T., Ruotsalainen, V., Hakola, P., Bakker, A. B. H., Phillips, J. H., Pekkarinen, P., et al. (2000) · Nature Genetics · doi:10.1038/77153 · Cited by 460 · see citing works
Oxidative stress in Alzheimer disease
Gella, A., & Durany, N. (2009) · Cell Adhesion & Migration · doi:10.4161/cam.3.1.7402 · Cited by 459 · see citing works
Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease
Jay, T. R., Hirsch, A. M., Broihier, M. L., Miller, C. M., Neilson, L. E., Ransohoff, R. M., Lamb, B. T., & Landreth, G. E. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2110-16.2016 · Cited by 457 · see citing works
Gowrishankar, S., Yuan, P., Wu, Y., Schrag, M., Paradise, S., Grutzendler, J., De Camilli, P., & Ferguson, S. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510329112 · Cited by 406 · see citing works
Wakselman, S., Béchade, C., Roumier, A., Bernard, D., Triller, A., & Bessis, A. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1006-08.2008 · Cited by 351 · see citing works
Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD
Sajikumar, S. (2004) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2004.03.003 · Cited by 341 · see citing works
SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis
Luthi‐Carter, R., Taylor, D. M., Pallos, J., Lambert, E., Amore, A. M., Parker, J. A., Moffitt, H., Smith, D. L., Runne, H., Gökçe, Ö., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002924107 · Cited by 338 · see citing works
Tomic, J. L., Pensalfini, A., Head, E., & Glabe, C. G. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.05.024 · Cited by 336 · see citing works
Self-citationJiang, T., Tan, L., Zhu, X.-C., Zhang, Q.-Q., Cao, L., Tan, M.-S., Gu, L.-Z., Wang, H.-F., Ding, Z.-Z., Zhang, Y.-D., et al. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.164 · Cited by 320 · see citing works
Monoclonal antibodies that target pathological assemblies of Aβ
Lambert, M. P., Velasco, P. T., Chang, L., Viola, K. L., Fernandez, S., Lacor, P. N., Khuon, D., Gong, Y., Bigio, E. H., Shaw, P., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04157.x · Cited by 314 · see citing works
Self-citationWang, M., Roussos, P., McKenzie, A., Zhou, X., Kajiwara, Y., Brennand, K. J., De Luca, G. C., Crary, J. F., Casaccia, P., Buxbaum, J. D., et al. (2016) · Genome Medicine · doi:10.1186/s13073-016-0355-3 · Cited by 314 · see citing works
Self-citationMisonou, H., Morishima-Kawashima, M., & Ihara, Y. (2000) · Biochemistry · doi:10.1021/bi000169p · Cited by 304 · see citing works
Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice
Li, F., Calingasan, N. Y., Yu, F., Mauck, W. M., Toidze, M., Almeida, C. G., Takahashi, R. H., Carlson, G. A., Beal, M. F., Lin, M. T. S., et al. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02455.x · Cited by 276 · see citing works
Inflammatory components in human Alzheimer’s disease and after active amyloid-β42 immunization
Zotova, E., Bharambe, V., Cheaveau, M., Morgan, W., Holmes, C., Harris, S., Neal, J. W., Love, S., Nicoll, J. A. R., & Boche, D. (2013) · Brain · doi:10.1093/brain/awt210 · Cited by 272 · see citing works
DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.
Bakker, A. B., Hoek, R., Cerwenka, A., Blom, B., Lucian, L., McNeil, T., Murray, R., Phillips, L., Sedgwick, J., & Lanier, L. (2000) · Immunity · doi:10.1016/s1074-7613(00)00034-0 · Cited by 269 · see citing works
Ca2+ Buffer Saturation Underlies Paired Pulse Facilitation in Calbindin-D28k-Containing Terminals
Blatow, M., Caputi, A., Burnashev, N., Monyer, H., & Rozov, A. V. (2003) · Neuron · doi:10.1016/s0896-6273(03)00196-x · Cited by 267 · see citing works
A Serum Protein–Based Algorithm for the Detection of Alzheimer Disease
O’Bryant, S. E. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.215 · Cited by 229 · see citing works
AMPA receptor downscaling at the onset of Alzheimer's disease pathology in double knockin mice
Chang, E. H., Savage, M. J., Flood, D. G., Thomas, J. M., Levy, R. B., Mahadomrongkul, V., Shirao, T., Aoki, C., & Huerta, P. T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507313103 · Cited by 225 · see citing works
Benarroch, E. E. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a4a577 · Cited by 222 · see citing works
Pedrós, I., Petrov, D., Allgaier, M., Sureda, F. X., Barroso, E., Beas‐Zárate, C., Auladell, C., Pallàs, M., Vázquez‐Carrera, M., Casadesús, G., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.05.025 · Cited by 203 · see citing works
Barnes maze, a useful task to assess spatial reference memory in the mice
Sunyer, B., Patil, S. S., Höger, H., & Luber, G. (2007) · Protocol Exchange · doi:10.1038/nprot.2007.390 · Cited by 201 · see citing works
Kiddle, S. J., Sattlecker, M., Proitsi, P., Simmons, A., Westman, E., Bazenet, C. E., Nelson, S. K., Williams, S., Hodges, A., Johnston, C., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130380 · Cited by 187 · see citing works
TREM2 modifies microglial phenotype and provides neuroprotection in P301S tau transgenic mice
Jiang, T., Zhang, Y.-D., Chen, Q., Gao, Q., Zhu, X.-C., Zhou, J.-S., Shi, J.-Q., Lu, H., Tan, L., & Yu, J.-T. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.01.028 · Cited by 176 · see citing works
Akt activity in Alzheimer’s disease and other neurodegenerative disorders
Rickle, A., Bogdanović, N., Volkmann, I., Winblad, B. G., Ravid, R., & Cowburn, R. F. (2004) · Neuroreport · doi:10.1097/00001756-200404290-00005 · Cited by 166 · see citing works
CD33 modulates TREM2: convergence of Alzheimer loci
Chan, G., White, C. C., Winn, P. A., Cimpean, M., Replogle, J. M., Glick, L. R., Cuerdon, N. E., Ryan, K. J., Johnson, K. A., Schneider, J. A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4126 · Cited by 162 · see citing works
Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function
Roumier, A., Pascual, O., Béchade, C., Wakselman, S., Poncer, J.-C., Réal, E., Triller, A., & Bessis, A. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002595 · Cited by 146 · see citing works
Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration
Liu, P., Reed, M. N., Kotilinek, L., Grant, M. K. O., Forster, C. L., Qiang, W., Shapiro, S. L., Reichl, J. H., Chiang, A. C. A., Jankowsky, J. L., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.021 · Cited by 143 · see citing works
Arisi, I., D’Onofrio, M., Brandi, R., Felsani, A., Capsoni, S., Drovandi, G., Felici, G., Weitschek, E., Bertolazzi, P., & Cattaneo, A. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101881 · Cited by 139 · see citing works
Li, X., Long, J., He, T., Belshaw, R. D., & Scott, J. (2015) · Scientific Reports · doi:10.1038/srep12393 · Cited by 138 · see citing works
Marchetti, C., & Marie, H. (2011) · Reviews in the Neurosciences · doi:10.1515/rns.2011.035 · Cited by 133 · see citing works
A key role for TGF-β1 in hippocampal synaptic plasticity and memory
Caraci, F., Gulisano, W., Guida, C. A., Impellizzeri, A. A. R., Drago, F., Puzzo, D., & Palmeri, A. (2015) · Scientific Reports · doi:10.1038/srep11252 · Cited by 126 · see citing works
Missense variant in TREML2 protects against Alzheimer's disease
Benítez, B. A., Jin, S. C., Guerreiro, R. J., Graham, R., Lord, J., Harold, D. H., Sims, R., Lambert, J., Gibbs, J. R., Brás, J., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.12.010 · Cited by 122 · see citing works
Jiang, T., Tan, L., Zhu, X.-C., Zhou, J.-S., Cao, L., Tan, M.-S., Wang, H.-F., Chen, Q., Zhang, Y.-D., & Yu, J.-T. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.08.019 · Cited by 111 · see citing works
Neuroprotective Effect of TREM-2 in Aging and Alzheimer’s Disease Model
Raha, A. A., Henderson, J. W., Stott, S., Vuono, R., Foscarin, S., Friedland, R. P., Zaman, S. H., & Raha‐Chowdhury, R. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160663 · Cited by 109 · see citing works
The AAA+ ATPase, Thorase Regulates AMPA Receptor-Dependent Synaptic Plasticity and Behavior
Zhang, J., Wang, Y., Chi, Z., Keuss, M. J., Pai, Y.-M. E., Kang, H., Shin, J.-H., Bugayenko, A., Wang, H., Xiong, Y., et al. (2011) · Cell · doi:10.1016/j.cell.2011.03.016 · Cited by 94 · see citing works
TYROBP genetic variants in early-onset Alzheimer's disease
Pottier, C., Ravenscroft, T. A., Brown, P. H., Finch, N. A., Baker, M., Parsons, M., Asmann, Y. W., Ren, Y., Christopher, E., Levitch, D., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.028 · Cited by 94 · see citing works
Walker, D. G., Whetzel, A. M., Serrano, G., Sue, L. I., Beach, T. G., & Lue, L.-F. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.023 · Cited by 93 · see citing works
Yang, W., Zhou, X., Zimmermann, H. R., Cavener, D. R., Klann, E., & Ma, T. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.02.005 · Cited by 87 · see citing works
Initiative, A. D. N., Takahashi, H., Klein, Z. A., Bhagat, S. M., Kaufman, A. C., Kostylev, M. A., Ikezu, T., & Strittmatter, S. M. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1668-z · Cited by 83 · see citing works
Fanutza, T., Prete, D. D., Ford, M. J., Castillo, P. E., & D'adamio, L. (2015) · eLife · doi:10.7554/elife.09743 · Cited by 81 · see citing works
Self-citationMicroglia as Dynamic and Essential Components of the Amyloid Hypothesis
Gandy, S., & Heppner, F. L. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.007 · Cited by 73 · see citing works
Self-citationGal, J., Bang, Y., & Choi, H. J. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.07.010 · Cited by 69 · see citing works
Mueller, C., Zhou, W., VanMeter, A., Heiby, M., Magaki, S., Ross, M. M., Espina, V. A., Schrag, M., Dickson, C., Liotta, L. A., et al. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1303 · Cited by 63 · see citing works
Cathepsin D gene and the risk of Alzheimer's disease: A population-based study and meta-analysis
Schuur, M., Ikram, M. A., Swieten, J. C. V., Isaacs, A. J., Vergeer, J. M., Albert Hofman, D., Oostra, B. A., Breteler, M. M. B., & van Duijn, C. M. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.10.011 · Cited by 60 · see citing works
Effective anti-Alzheimer Aβ therapy involves depletion of specific Aβ oligomer subtypes
Knight, E. M., Kim, S. H., Kottwitz, J., Hatami, A., Albay, R., Suzuki, A. Z., Lublin, A. L., Alberini, C. M., Klein, W. L., Szabo, P., et al. (2016) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000237 · Cited by 47 · see citing works
Self-citationJiang, T., Wan, Y., Zhang, Y.-D., Zhou, J.-S., Gao, Q., Zhu, X.-C., Shi, J.-Q., Lu, H., Tan, L., & Yu, J.-T. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-9704-x · Cited by 46 · see citing works
Davidson, Y. (2006) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2005.063917 · Cited by 45 · see citing works
The SIRT2 Polymorphism rs10410544 and Risk of Alzheimer’s Disease: A Meta-analysis
Wei, W., Xu, X., Li, H., Zhang, Y., Han, D., Wang, Y., Yan, W., Wang, X., Zhang, J., Liu, N., et al. (2014) · NeuroMolecular Medicine · doi:10.1007/s12017-014-8291-0 · Cited by 29 · see citing works
Knight, E. M., Ruiz, H. H., Kim, S. H., Harte, J. C., Hsieh, W., Glabe, C. G., Klein, W. L., Attie, A., Buettner, C., Ehrlich, M. E., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0282-y · Cited by 25 · see citing works
Self-citationElucidating Molecular Mass and Shape of a Neurotoxic Aβ Oligomer
Sebollela, A. S., Mustata, G.-M., Luo, K., Velasco, P. T., Viola, K. L., Cline, E. N., Shekhawat, G. S., Wilcox, K. C., Dravid, V. P., & Klein, W. L. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500156r · Cited by 25 · see citing works
Self-citationLiu, S., Zhao, H., Wang, J., Huang, T., Tian, H., Yao, L., Tao, H., Chen, Z., Wang, C., Sheng, S., et al. (2015) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12430 · Cited by 21 · see citing works
Readhead, B., Haure‐Mirande, J., Zhang, B., Haroutunian, V. H., Gandy, S., Schadt, E. E., Dudley, J. T., & Ehrlich, M. E. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.167 · Cited by 14 · see citing works
Self-citationSayad, A., Noruzinia, M., Zamani, M., Harirchian, M. H., & Kazemnejad, A. (2013) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000347128 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Applications of machine learning to diagnosis and treatment of neurodegenerative diseases
Myszczynska, M. A., Ojamies, P. N., Lacoste, A. M. B., Neil, D., Saffari, A., Mead, R., Hautbergue, G. M., Holbrook, J. D., & Ferraiuolo, L. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0377-8 · Cited by 595 · see citing works
Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Newcombe, E. A., Camats-Perna, J., Silva, M. L., Valmas, N., Huat, T. J., & Medeiros, R. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1313-3 · Cited by 532 · see citing works
TREM2 in Neurodegenerative Diseases
Jay, T. R., von Saucken, V. E., & Landreth, G. E. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0197-5 · Cited by 427 · see citing works
Tau and neuroinflammation: what impact for Alzheimer's disease and tauopathies?
Laurent, C., Buée, L., & Blum, D. (2018) · Biomedical Journal · doi:10.1016/j.bj.2018.01.003 · Cited by 348 · see citing works
The identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308 · see citing works
Novel Approaches for the Treatment of Alzheimer’s and Parkinson’s Disease
Bulck, M. V., Sierra‐Magro, A., Alarcón-Gil, J., Pérez‐Castillo, A., & Morales-Garcia, J. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030719 · Cited by 179 · see citing works
Multiscale causal networks identify VGF as a key regulator of Alzheimer’s disease
Beckmann, N. D., Lin, W.-J., Wang, M., Cohain, A. T., Charney, A. W., Wang, P., Ma, W., Wang, Y.-C., Jiang, C., Audrain, M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17405-z · Cited by 172 · see citing works
Self-citationHaure-Mirande, J.-V., Audrain, M., Ehrlich, M. E., & Gandy, S. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00552-w · Cited by 159 · see citing works
Self-citationMicroglial priming of antigen presentation and adaptive stimulation in Alzheimer’s disease
Das, R., & Chinnathambi, S. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03132-2 · Cited by 147 · see citing works
Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello, C., Yuan, P., & Grutzendler, J. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.10.007 · Cited by 131 · see citing works
TREM2: Potential therapeutic targeting of microglia for Alzheimer's disease
Li, Y., Xu, H., Wang, H., Yang, K., Luan, J., & Wang, S. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115218 · Cited by 128 · see citing works
Significance of Complement System in Ischemic Stroke: A Comprehensive Review
Ma, Y., Liu, Y., Zhang, Z., & Yang, G. (2019) · Aging and Disease · doi:10.14336/ad.2019.0119 · Cited by 122 · see citing works
Microglia in neurodegenerative diseases
Xu, Y., Jin, M.-Z., Yang, Z., & Jin, M.-Z. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.290881 · Cited by 118 · see citing works
CD33 in Alzheimer’s Disease – Biology, Pathogenesis, and Therapeutics: A Mini-Review
Zhao, L. (2018) · Gerontology · doi:10.1159/000492596 · Cited by 124 · see citing works
Weng, Y., Wang, H., Li, L., Feng, Y., Xu, S., & Wang, Z. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101849 · Cited by 114 · see citing works
TREM2 triggers microglial density and age-related neuronal loss
Linnartz‐Gerlach, B., Bodea, L., Klaus, C., Ginolhac, A., Halder, R., Sinkkonen, L., Walter, J., Colonna, M., & Neumann, H. (2019) · Glia · doi:10.1002/glia.23563 · Cited by 104 · see citing works
The landscape of multiscale transcriptomic networks and key regulators in Parkinson’s disease
Wang, Q., Zhang, Y., Wang, M., Song, W.-M., Shen, Q., McKenzie, A., Choi, I., Zhou, X., Pan, P.-Y., Yue, Z., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13144-y · Cited by 121 · see citing works
Self-citationPatir, A., Shih, B., McColl, B. W., & Freeman, T. C. (2019) · Glia · doi:10.1002/glia.23572 · Cited by 90 · see citing works
Haure-Mirande, J.-V., Wang, M., Audrain, M., Fanutza, T., Kim, S. H., Heja, S., Readhead, B., Dudley, J. T., Blitzer, R. D., Schadt, E. E., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0255-6 · Cited by 84 · see citing works
Self-citationde Vries, L. E., Huitinga, I., Kessels, H. W. H. G., Swaab, D. F., & Verhaagen, J. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00719-7 · Cited by 82 · see citing works
Castranio, E. L., Hasel, P., Haure‐Mirande, J., Ramirez Jimenez, A. V., Hamilton, B. W., Kim, R. D., Glabe, C. G., Wang, M., Zhang, B., Gandy, S., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12821 · Cited by 74 · see citing works
“49, 53,54,56 A similar interpretation could be developed from the studies of Trem2 deficiency, as differences were dependent on early versus later disease stages.”
Self-citationKazim, S. F., Sharma, A., Saroja, S. R., Seo, J. H., Larson, C. S., Ramakrishnan, A., Wang, M., Blitzer, R. D., Shen, L., Peña, C. J., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.02.973 · Cited by 72 · see citing works
Self-citationTrem2 deficiency differentially affects phenotype and transcriptome of human APOE3 and APOE4 mice
Fitz, N. F., Wolfe, C. M., Playso, B. E., Biedrzycki, R. J., Lu, Y., Nam, K. N., Lefterov, I., & Koldamova, R. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00394-4 · Cited by 68 · see citing works
Audrain, M., Haure-Mirande, J.-V., Wang, M., Kim, S. H., Fanutza, T., Chakrabarty, P., Fraser, P., St George-Hyslop, P. H., Golde, T. E., Blitzer, R. D., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0258-3 · Cited by 68 · see citing works
Self-citationAudrain, M., Haure‐Mirande, J., Mleczko, J., Wang, M., Griffin, J. K., St George‐Hyslop, P. H., Fraser, P., Zhang, B., Gandy, S., & Ehrlich, M. E. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12256 · Cited by 65 · see citing works
Self-citationThe Importance of Complement-Mediated Immune Signaling in Alzheimer’s Disease Pathogenesis
Batista, A. F., Khan, K., Papavergi, M.-T., & Lemere, C. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020817 · Cited by 67 · see citing works
Modulation of C5a–C5aR1 signaling alters the dynamics of AD progression
Carvalho, K., Schartz, N. D., Balderrama-Gutierrez, G., Liang, H. Y., Chu, S., Selvan, P., Gómez-Arboledas, Á., Petrisko, T. J., Fonseca, M. I., Mortazavi, A., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02539-2 · Cited by 59 · see citing works
Zhou, Y., Tada, M., Cai, Z., Andhey, P. S., Swain, A., Miller, K. R., Gilfillan, S., Artyomov, M. N., Takao, M., Kakita, A., et al. (2023) · Nature Immunology · doi:10.1038/s41590-022-01403-y · Cited by 61 · see citing works
Souchet, B., Audrain, M., Billard, J. M., Dairou, J., Fol, R. R., Orefice, N. S., Tada, S., Gu, Y., Dufayet‐Chaffaud, G., Limanton, E., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0678-6 · Cited by 55 · see citing works
Self-citationTran, K. M., Kawauchi, S., Kramár, E. A., Rezaie, N., Liang, H. Y., Sakr, J., Gómez-Arboledas, Á., Arreola, M. A., da Cunha, C., Phan, J., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00598-4 · Cited by 50 · see citing works
Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer’s disease
Serrano-Pozo, A., Li, Z., Noori, A., Nguyen, H. N., Mezlini, A., Li, L., Hudry, E., Jackson, R. J., Hyman, B. T., & Das, S. (2021) · Nature Aging · doi:10.1038/s43587-021-00123-6 · Cited by 49 · see citing works
Wang, Q., Liu, J., Zhang, Y., Li, Z., Zhao, Z., Jiang, W., Zhao, J., Hou, L., & Wang, Q. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103369 · Cited by 49 · see citing works
Transcriptional Networks of Microglia in Alzheimer’s Disease and Insights into Pathogenesis
Chew, G., & Petretto, E. G. (2019) · Genes · doi:10.3390/genes10100798 · Cited by 45 · see citing works
Control of Innate Immunity by Sialic Acids in the Nervous Tissue
Liao, H., Klaus, C., & Neumann, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21155494 · Cited by 46 · see citing works
Harnessing Immunoproteostasis to Treat Neurodegenerative Disorders
Golde, T. E. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.027 · Cited by 45 · see citing works
Complement in Neurologic Disease
Propson, N. E., Gedam, M., & Zheng, H. (2020) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-031620-113409 · Cited by 43 · see citing works
Martínez‐Mármol, R., Chai, Y., Conroy, J. N., Khan, Z., Hong, S., Kim, S. B., Gormal, R. S., Lee, D. H., Lee, J. K., Coulson, E. J., et al. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15767 · Cited by 42 · see citing works
Self-citationMartin, N. A., Nawrocki, A., Molnár, V., Elkjaer, M. L., Thygesen, E. K., Palkovits, M., Ács, P., Sejbæk, T., Nielsen, H. H., Hegedüs, Z., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0202530 · Cited by 41 · see citing works
Bioinformatic analysis identifies key transcriptome signatures in temporal lobe epilepsy
Chen, Q., Xia, L., Zhong, S., Wang, Q., Ding, J., & Wang, X. (2020) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13470 · Cited by 42 · see citing works
Early onset senescence and cognitive impairment in a murine model of repeated mTBI
Schwab, N., Ju, Y., & Hazrati, L.-N. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01190-x · Cited by 39 · see citing works
Sekiya, M., Wang, M., Fujisaki, N., Sakakibara, Y., Quan, X., Ehrlich, M. E., De Jager, P. L., Bennett, D. A., Schadt, E. E., Gandy, S., et al. (2018) · Genome Medicine · doi:10.1186/s13073-018-0530-9 · Cited by 38 · see citing works
Self-citationINPP5D modulates TREM2 loss-of-function phenotypes in a β-amyloidosis mouse model
Iguchi, A., Takatori, S., Kimura, S., Muneto, H., Wang, K., Etani, H., Ito, G., Sato, H., Hori, Y., Sasaki, J., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106375 · Cited by 37 · see citing works
Natural killer cells in the central nervous system
Ning, Z., Liu, Y., Guo, D., Lin, W., & Tang, Y. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01324-9 · Cited by 40 · see citing works
miR155 regulation of behavior, neuropathology, and cortical transcriptomics in Alzheimer's disease
Readhead, B., Haure-Mirande, J.-V., Mastroeni, D., Audrain, M., Fanutza, T., Kim, S. H., Blitzer, R. D., Gandy, S., Dudley, J. T., & Ehrlich, M. E. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02185-z · Cited by 37 · see citing works
Self-citationMicroglial TREM2 at the Intersection of Brain Aging and Alzheimer’s Disease
Qu, W., & Li, L. (2021) · The Neuroscientist · doi:10.1177/10738584211040786 · Cited by 37 · see citing works
Etxeberria, A., Shen, Y.-A. A., Vito, S., Silverman, S. M., Imperio, J., Lalehzadeh, G., Soung, A. L., Du, C., Xie, L., Choy, M. K., et al. (2024) · The Journal of Neuroscience · doi:10.1523/jneurosci.2347-23.2024 · Cited by 34 · see citing works
Mauduit, O., Delcroix, V., Umazume, T., de Paiva, C. S., Dartt, D. A., & Makarenkova, H. P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1011125 · Cited by 29 · see citing works
de Vries, L. E., Jongejan, A., Fortes, J. M., Balesar, R. A., Rozemüller, A. J. M., Moerland, P. D., Huitinga, I., Swaab, D. F., & Verhaagen, J. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01760-9 · Cited by 28 · see citing works
Osteoporosis and Alzheimer´s disease (or Alzheimer´s disease and Osteoporosis)
Wanionok, N. E., Morel, G. R., & Fernández, J. M. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102408 · Cited by 30 · see citing works
The Microglial Response to Neurodegenerative Disease
Song, W. M., & Colonna, M. (2018) · Advances in immunology · doi:10.1016/bs.ai.2018.04.002 · Cited by 28 · see citing works
Martínez‐Mármol, R., Mohannak, N., Qian, L., Wang, T., Gormal, R. S., Ruitenberg, M. J., Vanhaesebroeck, B., Coulson, E. J., & Meunier, F. A. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.0674-19.2019 · Cited by 28 · see citing works
Kim, B., Dabin, L. C., Tate, M. D., Karahan, H., Sharify, A. D., Acri, D. J., Al-Amin, M. M., Philtjens, S., Smith, D. C., Wijeratne, H. R. S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48484-x · Cited by 28 · see citing works
Zhou, W., He, J., Shen, G., Liu, Y., Zhao, P., & Li, J. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07002-z · Cited by 28 · see citing works
Johnson, T. S., Xiang, S., Dong, T., Huang, Z., Cheng, M., Wang, T., Yang, K., Ni, D., Huang, K., & Zhang, J. (2021) · Scientific Reports · doi:10.1038/s41598-020-79740-x · Cited by 26 · see citing works
Neuronal hibernation following hippocampal demyelination
Baltan, S., Jawaid, S., Chomyk, A. M., Kidd, G. J., Chen, J. M., Battapady, H. D., Chan, R., Dutta, R., & Trapp, B. D. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01130-9 · Cited by 25 · see citing works
Knowledge gaps in Alzheimer's disease immune biomarker research
Morgan, D., & Mielke, M. M. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12342 · Cited by 25 · see citing works
Berberine modulates microglial polarization by activating TYROBP in Alzheimer's disease
Yu, Y., Wu, J., Jia, L., Feng, S., Qi, Z., Yu, H., Wu, Y., & Wang, S. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156237 · Cited by 24 · see citing works
Savarin, C., Dutta, R., & Bergmann, C. C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01325 · Cited by 25 · see citing works
Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases
Prasad, H., & Rao, R. (2020) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2020_25 · Cited by 25 · see citing works
Generation of rat forebrain tissues in mice
Huang, J., He, B., Yang, X., Long, X., Wei, Y., Li, L., Tang, M., Gao, Y., Fang, Y., Ying, W., et al. (2024) · Cell · doi:10.1016/j.cell.2024.03.017 · Cited by 27 · see citing works
Alzheimer's disease pathology in Nasu-Hakola disease brains
Satoh, J., Kino, Y., Yanaizu, M., & Saito, Y. (2018) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2017.01088 · Cited by 24 · see citing works
Tangavelou, K., & Bhaskar, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252212335 · Cited by 24 · see citing works
Lv, Z., Xu, T., Li, R., Zheng, D., Li, Y., Li, W., Yang, Y. X., & Hao, Y. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.739201 · Cited by 22 · see citing works
Zhao, Y., Guo, Q., Tian, J., Liu, W., & Wang, X. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102596 · Cited by 22 · see citing works
Current understanding on TREM-2 molecular biology and physiopathological functions
Bharadwaj, S., Groza, Y., Mierzwicka, J. M., & Malý, P. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112042 · Cited by 22 · see citing works
Su, Y., Li, H., Zhang, W., Tao, S., Wang, Q., Zhang, X., Zhou, M., Huang, X., Wang, C., Tang, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60746-w · Cited by 25 · see citing works
Kim, J., Selvaraji, S., Kang, S. W., Lee, W. T., Chen, C., Choi, H., Koo, E. H., Jo, D., Lim, K. L., Lim, Y.-A., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.04.011 · Cited by 20 · see citing works
Creus‐Muncunill, J., Haure‐Mirande, J., Mattei, D., Bons, J., Jimenez, A. V. R., Hamilton, B. W., Corwin, C., Chowdhury, S., Schilling, B., Ellerby, L., et al. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03052-4 · Cited by 20 · see citing works
Self-citationBiagioli, M., Mencarelli, A., Carino, A., Cipriani, S., Marchianò, S., Fiorucci, C., Donini, A., Graziosi, L., Baldelli, F., Distrutti, E., et al. (2017) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izx031 · Cited by 20 · see citing works
The Dual Nature of Microglia in Alzheimer’s Disease: A Microglia-Neuron Crosstalk Perspective
Xie, Z., Meng, J., Wu, Z., Nakanishi, H., Hayashi, Y., Kong, W., Lan, F., Narengaowa, Yang, Q., Qing, H., et al. (2022) · The Neuroscientist · doi:10.1177/10738584211070273 · Cited by 20 · see citing works
Peng, W., Xie, Y., Liao, C., Bai, Y., Wang, H., & Li, C. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.966153 · Cited by 18 · see citing works
Tyagi, A., Musa, M., Labeikovsky, W., & Pugazhenthi, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-23652-5 · Cited by 17 · see citing works
Myeloid lineage C3 induces reactive gliosis and neuronal stress during CNS inflammation
Garton, T. P., Smith, M. D., Kesharwani, A., Gharagozloo, M., Oh, S., Na, C. H., Absinta, M., Reich, D. S., Zack, D. J., & Calabresi, P. A. (2025) · Nature Communications · doi:10.1038/s41467-025-58708-3 · Cited by 18 · see citing works
Wang, T., Wu, B., Zhang, X., Zhang, M., Zhang, S., Huang, W., Liu, T., Yu, W., Li, J., & Yu, X. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27908 · Cited by 13 · see citing works
An Integrated Molecular Atlas of Alzheimer’s DiseasePreprint
Wörheide, M. A., Krumsiek, J., Nataf, S., Nho, K. T., Greenwood, A. K., Wiley, J. C., Willruth, L.-L., Wu, T., Bellur, O., Marella, B., et al. (2021) · medRxiv · doi:10.1101/2021.09.14.21263565 · Cited by 12 · see citing works
How Microglia Manages Non-cell Autonomous Vicious Cycling of Aβ Toxicity in the Pathogenesis of AD
Seol, Y., Ki, S., Ryu, H. L., Chung, S., Lee, J.-H., & Ryu, H. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.593724 · Cited by 12 · see citing works
Multiscale causal network models of Alzheimer’s disease identify VGF as a key regulator of diseasePreprint
Beckmann, N. D., Lin, W., Wang, M., Cohain, A. T., Wang, P., Ma, W., Wang, Y., Jiang, C. S., Audrain, M., Comella, P., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/458430 · Cited by 12 · see citing works
Self-citationGammie, S. C., Messing, A., Hill, M. A., Kelm‐Nelson, C. A., & Hagemann, T. L. (2024) · PLoS ONE · doi:10.1371/journal.pone.0291995 · Cited by 11 · see citing works
Monoallelic TYROBP deletion is a novel risk factor for Alzheimer’s disease
Martiskainen, H., Willman, R.-M., Harju, P., Heikkinen, S., Heiskanen, M., Müller, S. A., Sinisalo, R., Takalo, M., Mäkinen, P. M., Kuulasmaa, T., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00830-3 · Cited by 14 · see citing works
Ashford, B., Simpson, J. E., Dawson, C., Boche, D., Cooper‐Knock, J., Heath, P. R., Fillingham, D. J., Appleby‐Mallinder, C., Wei, W., Dunning, M., et al. (2025) · Brain Pathology · doi:10.1111/bpa.70019 · Cited by 13 · see citing works
S, H. S. G. N., Prasanna, V. L., Satish, K. S., Yergolkar, A. V., Krishnamurthy, M., Rajalekshmi, S. G., Radhika, K., & Burri, R. R. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101421 · Cited by 10 · see citing works
(2021) · Alzheimer s & Dementia · doi:10.1002/alz.12490 · Cited by 9 · see citing works
Chen, H., Fan, L., Guo, Q., Wong, M. Y., Zhu, J., Foxe, N. R., Wang, W. T., Nessim, A., Carling, G., Liu, B., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00903-3 · Cited by 8 · see citing works
Self-citationA module of multifactor‐mediated dysfunction guides the molecular typing of coronary heart disease
Li, Y., Lin, M., Wang, K., Zhan, Y., Gu, W., Gao, G.-H., Huang, Y., Chen, Y., Huang, T., & Wang, J. (2020) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.1415 · Cited by 8 · see citing works
Yarani, R., Palasca, O., Doncheva, N. T., Anthon, C., Pilecki, B., Svane, C. A. B., Mirza, A. H., Litman, T., Holmskov, U., Bang‐Berthelsen, C. H., et al. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1081176 · Cited by 9 · see citing works
Carter, J. J., Gardner, J., Poling, B. P., Welch, M., Nemeno, J. G., Houghton, J. E., & Dix, R. D. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1009032 · Cited by 6 · see citing works
Li, H., Xie, Z., Tian, Y., Zhou, R., Yang, Y., Lin, B., Chen, S., Wu, J., Deng, Z., Li, J., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03318-0 · Cited by 6 · see citing works
Widjaya, M. A., Liu, C.-H., Lee, S., & Cheng, W. (2023) · Journal of Molecular Neuroscience · doi:10.1007/s12031-023-02152-9 · Cited by 5 · see citing works
Homma, H., Yoshioka, Y., Fujita, K., Shirai, S., Hama, Y., Komano, H., Saito, Y., Yabe, I., Okano, H., Sasaki, H., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-06066-z · Cited by 5 · see citing works
Liu, M., Li, S., Ma, C., Wang, X., Yu, S., Lin, H., Guan, Z., & Yang, L. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11781 · Cited by 5 · see citing works
Pashaei, S., Shabani, S., Mohammadi, S., Morozova‐Roche, L. A., Salari, N., Rahimi, Z., & Khodarahmi, R. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04253-2 · Cited by 4 · see citing works
TREM2 ‐Mediated Myeloid Cells Protect Against Pathological Choroidal Neovascularization
wang, T., Szczepan, M., Gregg, A. T., Wang, X., Smith, L. E. H., & Sun, Y. (2025) · The FASEB Journal · doi:10.1096/fj.202501793r · 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
Li, R., Lv, Z., Li, Y., Li, W., & Hao, Y. (2022) · Chinese Medical Sciences Journal · doi:10.24920/004059 · Cited by 4 · see citing works
Martínez‐Mármol, R., Chai, Y., Khan, Z., Kim, S. B., Hong, S. M., Gormal, R. S., Lee, D. H., Lee, J. K., Lee, M. K., Kim, S. Y., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.28.271676 · Cited by 4 · see citing works
Self-citationLuo, W., Chen, H., Fan, L., Guo, Q., Wong, M. Y., Yu, F., Foxe, N. R., Wang, W. T., Nessim, A., Carling, G., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3454358/v1 · Cited by 4 · see citing works
Self-citationMonoallelic TYROBP deletion is a novel risk factor for Alzheimer’s diseasePreprint
Martiskainen, H., Willman, R.-M., Heikkinen, S., Müller, S. A., Sinisalo, R., Takalo, M., Mäkinen, P. M., Kuulasmaa, T., Pekkala, V., del Rey, A. G., et al. (2024) · medRxiv · doi:10.1101/2024.05.09.24307099 · Cited by 4 · see citing works
Ageing and Alzheimer’s Disease
Ai, R., Jin, X., Tang, B., Yang, G., Niu, Z., & Fang, E. F. (2021) · Springer eBooks · doi:10.1007/978-3-030-58080-3_74-1 · Cited by 3 · see citing works
Zhang, M., Duan, Y., Gan, H. K., Jiang, N., Qin, L., Luo, Y., Palahati, A., He, Y., Li, C., & Zhai, X. (2024) · Scientific Reports · doi:10.1038/s41598-024-71132-9 · Cited by 3 · see citing works
Huang, J., He, B., Yang, X., Long, X., Wei, Y., Gao, Y., Fang, Y., Ying, W., Wang, Z., Li, C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.13.536774 · Cited by 3 · see citing works
- Authors
- Haure-Mirande, J.-V., Audrain, M., Fanutza, T., Kim, S. H., Klein, W. L., Glabe, C., Readhead, B., Dudley, J. T., Blitzer, R. D., Wang, M., Zhang, B., Schadt, E. E., Gandy, S., & Ehrlich, M. E.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Northwestern University (US)
- University of California, Irvine (US)
- Corresponding author
- Gandy, Sam
- Ehrlich, Michelle E.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2017-06-13
- Volume
- 134
- Issue
- 5
- Pages
- 769-788
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC5645450
- OpenAlex
- W2625865615
- Cited by
- 127
- References
- 88
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 22 · 2023: 11 · 2022: 12 · 2021: 15 · 2020: 22 · 2019: 11 · 2018: 14 · 2017: 3
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Acta Neuropathologica (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institute on Aging (AG046170)
- Louis B. Mayer foundation
- Cure Alzheimer's Fund
- BrightFocus Foundation (A2016482F)
- Sarah and Gideon Gartner Foundation
- Georgianne and Dr Reza Khatib Foundation
- Werber Family Foundation
- Jennifer and Scott Moskowitz Foundation
- Jane Martin and Stuart Katz Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- TYROBP, DAP12, TREM2, CD33, CR3, Alzheimer's disease, microglia, neuroinflammation, amyloid-beta, tau phosphorylation, neuritic dystrophy, learning deficits, neuroprotection, gene knockout, early Alzheimer's disease, cerebral amyloidosis
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Mutation, Phosphorylation, tau Proteins, Microglia, Mice, Knockout, Maze Learning, Adaptor Proteins, Signal Transducing, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
