[1]

van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, et al. 2023. Lecanemab in early Alzheimer's disease. New England Journal of Medicine 388:9−21

doi: 10.1056/nejmoa2212948
[2]

Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, et al. 2023. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 330:512−527

doi: 10.1001/jama.2023.13239
[3]

Long JM, Holtzman DM. 2019. Alzheimer disease: an update on pathobiology and treatment strategies. Cell 179:312−339

doi: 10.1016/j.cell.2019.09.001
[4]

DeTure MA, Dickson DW. 2019. The neuropathological diagnosis of Alzheimer's disease. Molecular Neurodegeneration 14:32

doi: 10.1186/s13024-019-0333-5
[5]

Leuzy A, Bollack A, Pellegrino D, Teunissen CE, La Joie R, et al. 2025. Considerations in the clinical use of amyloid PET and CSF biomarkers for Alzheimer's disease. Alzheimer's & Dementia 21:e14528

doi: 10.1002/alz.14528
[6]

van Dyck CH. 2018. Anti-amyloid-β monoclonal antibodies for Alzheimer's disease: pitfalls and promise. Biological Psychiatry 83:311−319

doi: 10.1016/j.biopsych.2017.08.010
[7]

Perneczky R, Jessen F, Grimmer T, Levin J, Flöel A, et al. 2023. Anti-amyloid antibody therapies in Alzheimer's disease. Brain 146:842−849

doi: 10.1093/brain/awad005
[8]

Lu LL, Suscovich TJ, Fortune SM, Alter G. 2018. Beyond binding: antibody effector functions in infectious diseases. Nature Reviews Immunology 18:46−61

doi: 10.1038/nri.2017.106
[9]

Weber F, Bohrmann B, Niewoehner J, Fischer JAA, Rueger P, et al. 2018. Brain shuttle antibody for Alzheimer's disease with attenuated peripheral effector function due to an inverted binding mode. Cell Reports 22:149−162

doi: 10.1016/j.celrep.2017.12.019
[10]

Bohrmann B, Baumann K, Benz J, Gerber F, Huber W, et al. 2012. Gantenerumab: a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-β. Journal of Alzheimer's Disease 28:49−69

doi: 10.3233/JAD-2011-110977
[11]

Chen SH, Tian DY, Shen YY, Cheng Y, Fan DY, et al. 2020. Amyloid-beta uptake by blood monocytes is reduced with ageing and Alzheimer's disease. Translational Psychiatry 10:423

doi: 10.1038/s41398-020-01113-9
[12]

Huang X, Fowler C, Li Y, Li QX, Sun J, et al. 2024. Clearance and transport of amyloid β by peripheral monocytes correlate with Alzheimer's disease progression. Nature Communications 15:7998

doi: 10.1038/s41467-024-52396-1
[13]

Morgan D. 2009. The role of microglia in antibody-mediated clearance of amyloid-beta from the brain. CNS & Neurological Disorders Drug Targets 8:7−15

doi: 10.2174/187152709787601821
[14]

Wilcock DM, DiCarlo G, Henderson D, Jackson J, Clarke K, et al. 2003. Intracranially administered anti-Aβ antibodies reduce β-amyloid deposition by mechanisms both independent of and associated with microglial activation. The Journal of Neuroscience 23:3745−3751

doi: 10.1523/JNEUROSCI.23-09-03745.2003
[15]

Bacskai BJ, Kajdasz ST, McLellan ME, Games D, Seubert P, et al. 2002. Non-Fc-mediated mechanisms are involved in clearance of amyloid-β in vivo by immunotherapy. The Journal of Neuroscience 22:7873−7878

doi: 10.1523/jneurosci.22-18-07873.2002
[16]

Das P, Howard V, Loosbrock N, Dickson D, Murphy MP, et al. 2003. Amyloid-β immunization effectively reduces amyloid deposition in FcRγ−/− knock-out mice. The Journal of Neuroscience 23:8532−8538

doi: 10.1523/jneurosci.23-24-08532.2003
[17]

Solomon B, Koppel R, Frankel D, Hanan-Aharon E. 1997. Disaggregation of Alzheimer β-amyloid by site-directed mAb. Proceedings of the National Academy of Sciences of the United States of America 94:4109−4112

doi: 10.1073/pnas.94.8.4109
[18]

Sun XY, Yu XL, Zhu J, Li LJ, Zhang L, et al. 2023. Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer's disease-like mouse model. Signal Transduction and Targeted Therapy 8:30

doi: 10.1038/s41392-022-01273-8
[19]

Bouter Y, Noguerola JSL, Tucholla P, Crespi GAN, Parker MW, et al. 2015. Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N-truncated Abeta in sporadic Alzheimer disease cases and mouse models. Acta Neuropathologica 130:713−729

doi: 10.1007/s00401-015-1489-x
[20]

Cummings JL, Cohen S, van Dyck CH, Brody M, Curtis C, et al. 2018. ABBY: a phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease. Neurology 90:e1889−e1897

doi: 10.1212/wnl.0000000000005550
[21]

Da Mesquita S, Papadopoulos Z, Dykstra T, Brase L, Farias FG, et al. 2021. Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy. Nature 593:255−260

doi: 10.1038/s41586-021-03489-0
[22]

Albertini G, Zielonka M, Cuypers ML, Snellinx A, Xu C, et al. 2026. The Alzheimer's therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia. Nature Neuroscience 29:100−110

doi: 10.1038/s41593-025-02125-8
[23]

Chen Y, Colonna M. 2021. Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice? The Journal of Experimental Medicine 218:e20202717

doi: 10.1084/jem.20202717
[24]

Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, et al. 2022. Microglia states and nomenclature: a field at its crossroads. Neuron 110:3458−3483

doi: 10.1016/j.neuron.2022.10.020
[25]

Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, et al. 2017. A unique microglia type associated with restricting development of Alzheimer's disease. Cell 169:1276−1290.e17

doi: 10.1016/j.cell.2017.05.018
[26]

Gao C, Jiang J, Tan Y, Chen S. 2023. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduction and Targeted Therapy 8:359

doi: 10.1038/s41392-023-01588-0
[27]

Cadiz MP, Gibson KA, Todd KT, Nascari DG, Massa N, et al. 2024. Aducanumab anti-amyloid immunotherapy induces sustained microglial and immune alterations. Journal of Experimental Medicine 221:e20231363

doi: 10.1084/jem.20231363
[28]

Hou J, Chen Y, Cai Z, Heo GS, Yuede CM, et al. 2024. Antibody-mediated targeting of human microglial leukocyte Ig-like receptor B4 attenuates amyloid pathology in a mouse model. Science Translational Medicine 16:eadj9052

doi: 10.1126/scitranslmed.adj9052
[29]

Millet A, Ledo JH, Tavazoie SF. 2024. An exhausted-like microglial population accumulates in aged and APOE4 genotype Alzheimer's brains. Immunity 57:153−170.e6

doi: 10.1016/j.immuni.2023.12.001
[30]

de Weerd L, Hummel S, Müller SA, Paris I, Sandmann T, et al. 2025. Early intervention anti-Aβ immunotherapy attenuates microglial activation without inducing exhaustion at residual plaques. Molecular Neurodegeneration 20:92

doi: 10.1186/s13024-025-00878-1
[31]

Wang S, Mustafa M, Yuede CM, Salazar SV, Kong P, et al. 2020. Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer's disease model. Journal of Experimental Medicine 217:e20200785

doi: 10.1084/jem.20200785
[32]

Wang S, Sudan R, Peng V, Zhou Y, Du S, et al. 2022. TREM2 drives microglia response to amyloid-β via SYK-dependent and-independent pathways. Cell 185:4153−4169.e19

doi: 10.1016/j.cell.2022.09.033
[33]

Long H, Simmons A, Mayorga A, Burgess B, Nguyen T, et al. 2024. Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease. Alzheimer's Research & Therapy 16:235

doi: 10.1186/s13195-024-01599-1
[34]

Gratuze M, Schlachetzki JCM, D'Oliveira Albanus R, Jain N, Novotny B, et al. 2023. TREM2-independent microgliosis promotes tau-mediated neurodegeneration in the presence of ApoE4. Neuron 111:202−219.e7

doi: 10.1016/j.neuron.2022.10.022
[35]

Shi Y, Yamada K, Liddelow SA, Smith ST, Zhao L, et al. 2017. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549:523−527

doi: 10.1038/nature24016
[36]

Chen X, Firulyova M, Manis M, Herz J, Smirnov I, et al. 2023. Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy. Nature 615:668−677

doi: 10.1038/s41586-023-05788-0
[37]

Arthur-Farraj P, Loreto A. 2025. Targeting SARM1: from inhibition for neuroprotection to activation for neuroablation. Trends in Pharmacological Sciences 46:1105−1116

doi: 10.1016/j.tips.2025.09.003
[38]

Wang L, Liu Q, Li S, Wang N, Chen Y, et al. 2025. SARM1 senses dsDNA to promote NAD+ degradation and cell death. Cell 188:7137−7154.e21

doi: 10.1016/j.cell.2025.09.026
[39]

Mancuso R, Fattorelli N, Martinez-Muriana A, Davis E, Wolfs L, et al. 2024. Xenografted human microglia display diverse transcriptomic states in response to Alzheimer's disease-related amyloid-β pathology. Nature Neuroscience 27:886−900

doi: 10.1038/s41593-024-01600-y
[40]

Gate D, Saligrama N, Leventhal O, Yang AC, Unger MS, et al. 2020. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer's disease. Nature 577:399−404

doi: 10.1038/s41586-019-1895-7
[41]

Foss S, Sakya SA, Aguinagalde L, Lustig M, Shaughnessy J, et al. 2024. Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria. Nature Communications 15:2007

doi: 10.1038/s41467-024-46321-9
[42]

Wu D, Chen Q, Chen X, Han F, Chen Z, et al. 2023. The blood–brain barrier: structure, regulation and drug delivery. Signal Transduction and Targeted Therapy 8:217

doi: 10.1038/s41392-023-01481-w
[43]

Simonneau C, Duschmalé M, Gavrilov A, Brandenberg N, Hoehnel S, et al. 2021. Investigating receptor-mediated antibody transcytosis using blood–brain barrier organoid arrays. Fluids and Barriers of the CNS 18:43

doi: 10.1186/s12987-021-00276-x
[44]

Pizzo ME, Plowey ED, Khoury N, Kwan W, Abettan J, et al. 2025. Transferrin receptor–targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA. Science 389:eads3204

doi: 10.1126/science.ads3204
[45]

Chew KS, Wells RC, Moshkforoush A, Chan D, Lechtenberg KJ, et al. 2023. CD98hc is a target for brain delivery of biotherapeutics. Nature Communications 14:5053

doi: 10.1038/s41467-023-40681-4
[46]

Khoury N, Pizzo ME, Discenza CB, Joy D, Tatarakis D, et al. 2025. Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution. Nature Communications 16:1822

doi: 10.1038/s41467-025-57108-x
[47]

Okun E, Mattson MP, Arumugam TV. 2010. Involvement of Fc receptors in disorders of the central nervous system. Neuromolecular Medicine 12:164−178

doi: 10.1007/s12017-009-8099-5
[48]

Fuller JP, Stavenhagen JB, Teeling JL. 2014. New roles for Fc receptors in neurodegeneration-the impact on Immunotherapy for Alzheimer's Disease. Frontiers in Neuroscience 8:235

doi: 10.3389/fnins.2014.00235
[49]

van der Kleij H, Charles N, Karimi K, Mao YK, Foster J, et al. 2010. Evidence for neuronal expression of functional Fc (Epsilon and gamma) receptors. The Journal of Allergy and Clinical Immunology 125:757−760

doi: 10.1016/j.jaci.2009.10.054
[50]

Stamou M, Grodzki AC, van Oostrum M, Wollscheid B, Lein PJ. 2018. Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex. Journal of Neuroinflammation 15:7

doi: 10.1186/s12974-017-1050-z
[51]

Lan Y, Zhang X, Liu S, Guo C, Jin Y, et al. 2024. Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury. Immunity 57:349−363.e9

doi: 10.1016/j.immuni.2024.01.008
[52]

De Schepper S, Ge JZ, Crowley G, Ferreira LSS, Garceau D, et al. 2023. Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer's disease. Nature Neuroscience 26:406−415

doi: 10.1038/s41593-023-01257-z
[53]

Jauregui C, Blanco-Luquin I, Macías M, Roldan M, Caballero C, et al. 2023. Exploring the disease-associated microglia state in amyotrophic lateral sclerosis. Biomedicines 11:2994

doi: 10.3390/biomedicines11112994
[54]

Staszewski O, Hagemeyer N. 2019. Unique microglia expression profile in developing white matter. BMC Research Notes 12:367

doi: 10.1186/s13104-019-4410-1
[55]

Li Q, Cheng Z, Zhou L, Darmanis S, Neff NF, et al. 2019. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron 101:207−223.e10

doi: 10.1016/j.neuron.2018.12.006
[56]

Bill R, Wirapati P, Messemaker M, Roh W, Zitti B, et al. 2023. CXCL9: SPP1 macrophage polarity identifies a network of cellular programs that control human cancers. Science 381:515−524

doi: 10.1126/science.ade2292
[57]

Han H, Ge X, Komakula SSB, Desert R, Das S, et al. 2023. Macrophage-derived osteopontin (SPP1) protects from nonalcoholic steatohepatitis. Gastroenterology 165:201−217

doi: 10.1053/j.gastro.2023.03.228
[58]

Morse C, Tabib T, Sembrat J, Buschur KL, Bittar HT, et al. 2019. Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis. European Respiratory Journal 54:1802441

doi: 10.1183/13993003.02441-2018