{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:18:21Z","timestamp":1788873501250,"version":"build-2803163510"},"reference-count":109,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mamm Genome"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The brain and eye share striking anatomical, physiological, and immunological similarities. Both are protected by specialised vascular barriers, the blood-brain barrier (BBB) and blood-retinal barrier (BRB) respectively, that maintain homeostasis through tightly regulated cellular and molecular mechanisms. Increasing evidence implicates complement dysregulation as a key driver of neurodegeneration in both organs, contributing to disorders such as Alzheimer\u2019s disease (AD), and age-related macular degeneration (AMD). Genetic and molecular studies highlight overlapping mechanisms, with variants in complement regulators influencing susceptibility to both retinal and brain pathologies. Locally synthesised complement components modulate glial activation, vascular integrity, and synaptic remodelling at both sites and, when dysregulated, contribute to chronic inflammation, synapse loss and neuronal degradation. Despite these shared pathways, therapeutic development has progressed asymmetrically; several complement therapeutics are already in the clinic for AMD and other ocular pathologies, while none are yet in use for brain diseases. This is in part a consequence of the accessibility of the eye where complement targeted drugs can be directly delivered and impact on pathology monitored, difficult in the brain. Lessons learned from the eye, including local delivery to overcome challenges of barrier penetration, may help accelerate development of complement therapeutics for the brain. Here we present a brief perspective that integrates current understanding of complement-mediated mechanisms across brain and eye, emphasising clues from convergent pathophysiology and ocular translational successes.<\/jats:p>","DOI":"10.1007\/s00335-026-10199-3","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T12:35:54Z","timestamp":1770122154000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities"],"prefix":"10.1007","volume":"37","author":[{"given":"Jacqui","family":"Nimmo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Bright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura Elisabeth","family":"Nicholls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-7676","authenticated-orcid":false,"given":"Bryan Paul","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7782-1232","authenticated-orcid":false,"given":"Nikoleta","family":"Daskoulidou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2230-3550","authenticated-orcid":false,"given":"Wioleta Milena","family":"Zelek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"10199_CR1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/0165-5728(90)90055-R","volume":"30","author":"H Akiyama","year":"1990","unstructured":"Akiyama H, McGeer PL (1990) Brain microglia constitutively express \u03b2-2 integrins. J Neuroimmunol 30:81\u201393. https:\/\/doi.org\/10.1016\/0165-5728(90)90055-R","journal-title":"J Neuroimmunol"},{"key":"10199_CR2","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1038\/s41433-019-0501-4","volume":"33","author":"L Altay","year":"2019","unstructured":"Altay L, Sitnilska V, Schick T et al (2019) Early local activation of complement in aqueous humour of patients with age-related macular degeneration. Eye (Lond) 33:1859\u20131864. https:\/\/doi.org\/10.1038\/s41433-019-0501-4","journal-title":"Eye (Lond)"},{"key":"10199_CR3","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/S0002-9394(02)01624-0","volume":"134","author":"DH Anderson","year":"2002","unstructured":"Anderson DH, Mullins RF, Hageman GS, Johnson LV (2002) A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 134:411\u2013431. https:\/\/doi.org\/10.1016\/S0002-9394(02)01624-0","journal-title":"Am J Ophthalmol"},{"key":"10199_CR4","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1523\/JNEUROSCI.1854-18.2018","volume":"39","author":"SR Anderson","year":"2019","unstructured":"Anderson SR, Zhang J, Steele MR et al (2019) Complement Targets Newborn Retinal Ganglion Cells for Phagocytic Elimination by Microglia. J Neurosci 39:2025\u20132040. https:\/\/doi.org\/10.1523\/JNEUROSCI.1854-18.2018","journal-title":"J Neurosci"},{"key":"10199_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03304-3","volume":"21","author":"HU Banna","year":"2024","unstructured":"Banna HU, Slayo M, Armitage JA et al (2024) Imaging the eye as a window to brain health: frontier approaches and future directions. J Neuroinflammation 21:309. https:\/\/doi.org\/10.1186\/s12974-024-03304-3","journal-title":"J Neuroinflammation"},{"issue":"1","key":"10199_CR6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI144348","volume":"131","author":"K Bhatia","year":"2021","unstructured":"Bhatia K, Ahmad S, Kindelin A, Ducruet AF (2021) Complement C3a receptor-mediated vascular dysfunction: a complex interplay between aging and neurodegeneration. J Clin Invest 131(1):e144348. https:\/\/doi.org\/10.1172\/JCI144348","journal-title":"J Clin Invest"},{"key":"10199_CR7","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1007\/s12975-022-00993-x","volume":"13","author":"K Bhatia","year":"2022","unstructured":"Bhatia K, Kindelin A, Nadeem M et al (2022) Complement C3a Receptor (C3aR) Mediates Vascular Dysfunction, Hippocampal Pathology, and Cognitive Impairment in a Mouse Model of VCID. Transl Stroke Res 13:816\u2013829. https:\/\/doi.org\/10.1007\/s12975-022-00993-x","journal-title":"Transl Stroke Res"},{"key":"10199_CR8","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-025-00693-2","volume":"22","author":"G Bonvicini","year":"2025","unstructured":"Bonvicini G, Singh S, Sandersj\u00f6\u00f6 L et al (2025) High-affinity transferrin receptor binding improves brain delivery of bispecific antibodies at tracer dose. Fluids Barriers CNS 22:86. https:\/\/doi.org\/10.1186\/s12987-025-00693-2","journal-title":"Fluids Barriers CNS"},{"key":"10199_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01404-w","volume":"10","author":"SM Carpanini","year":"2022","unstructured":"Carpanini SM, Torvell M, Bevan RJ et al (2022) Terminal complement pathway activation drives synaptic loss in Alzheimer\u2019s disease models. Acta Neuropathol Commun 10:99. https:\/\/doi.org\/10.1186\/s40478-022-01404-w","journal-title":"Acta Neuropathol Commun"},{"key":"10199_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40681-4","volume":"14","author":"KS Chew","year":"2023","unstructured":"Chew KS, Wells RC, Moshkforoush A et al (2023) CD98hc is a target for brain delivery of biotherapeutics. Nat Commun 14:5053. https:\/\/doi.org\/10.1038\/s41467-023-40681-4","journal-title":"Nat Commun"},{"issue":"1","key":"10199_CR11","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3390\/jcm4010018","volume":"4","author":"SJ Clark","year":"2015","unstructured":"Clark SJ, Bishop PN (2015) Role of factor H and related proteins in regulating complement activation in the macula, and relevance to age-related macular degeneration. J Clin Med 4(1):18\u201331. https:\/\/doi.org\/10.3390\/jcm4010018","journal-title":"J Clin Med"},{"key":"10199_CR12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01778","volume":"8","author":"SJ Clark","year":"2017","unstructured":"Clark SJ, McHarg S, Tilakaratna V et al (2017) Bruch\u2019s membrane compartmentalizes complement regulation in the eye with implications for therapeutic design in age-related macular degeneration. Front Immunol 8:1778. https:\/\/doi.org\/10.3389\/fimmu.2017.01778","journal-title":"Front Immunol"},{"issue":"10","key":"10199_CR13","doi-asserted-by":"publisher","first-page":"4962","DOI":"10.4049\/jimmunol.1401613","volume":"193","author":"SJ Clark","year":"2014","unstructured":"Clark SJ, Schmidt CQ, White AM et al (2014) Identification of factor H-like protein 1 as the predominant complement regulator in Bruch\u2019s membrane: implications for age-related macular degeneration. J Immunol 193(10):4962\u201370. https:\/\/doi.org\/10.4049\/jimmunol.1401613","journal-title":"J Immunol"},{"key":"10199_CR14","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.nbd.2013.02.003","volume":"54","author":"H Crehan","year":"2013","unstructured":"Crehan H, Hardy J, Pocock J (2013) Blockage of CR1 prevents activation of rodent microglia. Neurobiol Dis 54:139\u2013149. https:\/\/doi.org\/10.1016\/j.nbd.2013.02.003","journal-title":"Neurobiol Dis"},{"key":"10199_CR15","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.bbrc.2017.09.019","volume":"494","author":"X Cui","year":"2017","unstructured":"Cui X, Zhang X, Bu H et al (2017) Shear stress-mediated changes in the expression of complement regulatory protein CD59 on human endothelial progenitor cells by ECM-integrin\u03b1V\u03b23-F-actin pathway in vitro. Biochem Biophys Res Commun 494:416\u2013421. https:\/\/doi.org\/10.1016\/j.bbrc.2017.09.019","journal-title":"Biochem Biophys Res Commun"},{"key":"10199_CR16","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/7854_2024_524","volume":"69","author":"N Daskoulidou","year":"2025","unstructured":"Daskoulidou N, Carpanini SM, Zelek WM, Morgan BP (2025a) Involvement of complement in Alzheimer\u2019s disease: from genetics through pathology to therapeutic strategies. Curr Top Behav Neurosci 69:3\u201324. https:\/\/doi.org\/10.1007\/7854_2024_524","journal-title":"Curr Top Behav Neurosci"},{"key":"10199_CR17","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1002\/glia.24355","volume":"71","author":"N Daskoulidou","year":"2023","unstructured":"Daskoulidou N, Shaw B, Torvell M et al (2023) Complement receptor 1 is expressed on brain cells and in the human brain. Glia 71:1522\u20131535. https:\/\/doi.org\/10.1002\/glia.24355","journal-title":"Glia"},{"key":"10199_CR18","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70458","volume":"21","author":"N Daskoulidou","year":"2025","unstructured":"Daskoulidou N, Shaw B, Zelek WM, Morgan BP (2025b) The Alzheimer\u2019s disease-associated complement receptor 1 variant confers risk by impacting glial phagocytosis. Alzheimers Dement 21:e70458. https:\/\/doi.org\/10.1002\/alz.70458","journal-title":"Alzheimers Dement"},{"key":"10199_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-018-0650-x","volume":"6","author":"J den Haan","year":"2018","unstructured":"den Haan J, Morrema THJ, Verbraak FD et al (2018) Amyloid-beta and phosphorylated tau in post-mortem Alzheimer\u2019s disease retinas. Acta Neuropathol Commun 6:147. https:\/\/doi.org\/10.1186\/s40478-018-0650-x","journal-title":"Acta Neuropathol Commun"},{"key":"10199_CR20","unstructured":"Edinburgh I (2025) AI to use high street eye tests to spot dementia risk | News. In: The University of Edinburgh. https:\/\/www.ed.ac.uk\/news\/ai-to-use-high-street-eye-tests-to-spot-dementia-risk. Accessed 23 Oct 2025"},{"key":"10199_CR21","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00685397","volume":"57","author":"P Eikelenboom","year":"1982","unstructured":"Eikelenboom P, Stam FC (1982) Immunoglobulins and complement factors in senile plaques. Acta Neuropathol 57:239\u2013242. https:\/\/doi.org\/10.1007\/BF00685397","journal-title":"Acta Neuropathol"},{"key":"10199_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-024-01627-0","volume":"16","author":"LS Eppenberger","year":"2024","unstructured":"Eppenberger LS, Li C, Wong D et al (2024) Retinal thickness predicts the risk of cognitive decline over five years. Alzheimers Res Ther 16:273. https:\/\/doi.org\/10.1186\/s13195-024-01627-0","journal-title":"Alzheimers Res Ther"},{"key":"10199_CR23","unstructured":"European Medicines Agency (2024a) Syfovre | European Medicines Agency (EMA). https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/syfovre. Accessed 23 Oct 2025"},{"key":"10199_CR24","unstructured":"European Medicines Agency (2024b) Izelvay | European Medicines Agency (EMA). https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/izelvay. Accessed 23 Oct 2025"},{"key":"10199_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2024.110170","volume":"250","author":"X Feng","year":"2025","unstructured":"Feng X, Zhang L, Jiao K et al (2025) Tracking astrocyte polarization in the retina in retinopathy of prematurity. Exp Eye Res 250:110170. https:\/\/doi.org\/10.1016\/j.exer.2024.110170","journal-title":"Exp Eye Res"},{"key":"10199_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/cc7710","volume":"13","author":"MA Flierl","year":"2009","unstructured":"Flierl MA, Stahel PF, Rittirsch D et al (2009) Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis. Crit Care 13:R12. https:\/\/doi.org\/10.1186\/cc7710","journal-title":"Crit Care"},{"key":"10199_CR27","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/ng.3448","volume":"48","author":"LG Fritsche","year":"2016","unstructured":"Fritsche LG, Igl W, Cooke Bailey JN et al (2016) A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet 48:134\u2013143. https:\/\/doi.org\/10.1038\/ng.3448","journal-title":"Nat Genet"},{"key":"10199_CR28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115834","volume":"24","author":"MY Garc\u00eda-Berm\u00fadez","year":"2023","unstructured":"Garc\u00eda-Berm\u00fadez MY, Vohra R, Freude K et al (2023) Potential retinal biomarkers in Alzheimer\u2019s disease. Int J Mol Sci 24:15834. https:\/\/doi.org\/10.3390\/ijms242115834","journal-title":"Int J Mol Sci"},{"key":"10199_CR29","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1001\/archophthalmol.2010.18","volume":"128","author":"KM Gehrs","year":"2010","unstructured":"Gehrs KM, Jackson JR, Brown EN et al (2010) Complement, Age-Related macular degeneration and a vision of the future. Arch Ophthalmol 128:349\u2013358. https:\/\/doi.org\/10.1001\/archophthalmol.2010.18","journal-title":"Arch Ophthalmol"},{"key":"10199_CR30","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1001\/jamaneurol.2023.2851","volume":"80","author":"A Genge","year":"2023","unstructured":"Genge A, van den Berg LH, Frick G et al (2023) Efficacy and safety of ravulizumab, a complement C5 inhibitor, in adults with amyotrophic lateral sclerosis: a randomized clinical trial. JAMA Neurol 80:1089\u20131097. https:\/\/doi.org\/10.1001\/jamaneurol.2023.2851","journal-title":"JAMA Neurol"},{"issue":"5","key":"10199_CR31","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1007\/s00401-021-02366-4","volume":"142","author":"M Gharagozloo","year":"2021","unstructured":"Gharagozloo M, Smith MD, Jin J et al (2021) Complement component 3 from astrocytes mediates retinal ganglion cell loss during neuroinflammation. Acta Neuropathol 142(5):899\u2013915. https:\/\/doi.org\/10.1007\/s00401-021-02366-4","journal-title":"Acta Neuropathol"},{"key":"10199_CR32","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1093\/brain\/awq080","volume":"133","author":"AJ Green","year":"2010","unstructured":"Green AJ, McQuaid S, Hauser SL et al (2010) Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain 133:1591\u20131601. https:\/\/doi.org\/10.1093\/brain\/awq080","journal-title":"Brain"},{"key":"10199_CR33","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2023.2261509","volume":"15","author":"HP Grimm","year":"2023","unstructured":"Grimm HP, Schumacher V, Sch\u00e4fer M et al (2023) Delivery of the Brainshuttle<Superscript>\u2122<\/Superscript> amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans. MAbs 15:2261509. https:\/\/doi.org\/10.1080\/19420862.2023.2261509","journal-title":"MAbs"},{"key":"10199_CR34","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.2.3","volume":"64","author":"A Grover","year":"2023","unstructured":"Grover A, Sankaranarayanan S, Mathur V et al (2023) Pharmacokinetic and target engagement measures of ANX007, an anti-C1q antibody fragment, following intravitreal administration in nonhuman primates. Invest Ophthalmol Vis Sci 64:3. https:\/\/doi.org\/10.1167\/iovs.64.2.3","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10199_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-025-03458-5","volume":"15","author":"F Guo","year":"2025","unstructured":"Guo F, Sheng Z-H, Fu Y et al (2025) Complement C1q is associated with neuroinflammation and mediates the association between amyloid-\u03b2 and tau pathology in Alzheimer\u2019s disease. Transl Psychiatry 15:247. https:\/\/doi.org\/10.1038\/s41398-025-03458-5","journal-title":"Transl Psychiatry"},{"issue":"6","key":"10199_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114299","volume":"43","author":"KA Guttenplan","year":"2024","unstructured":"Guttenplan KA, Stafford BK, El-Danaf RN et al (2024) Neurotoxic reactive astrocytes drive neuronal death after retinal injury. Cell Rep 43(6):114299. https:\/\/doi.org\/10.1016\/j.celrep.2024.114299","journal-title":"Cell Rep"},{"issue":"7883","key":"10199_CR37","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41586-021-03960-y","volume":"599","author":"KA Guttenplan","year":"2021","unstructured":"Guttenplan KA, Weigel MK, Prakash P et al (2021) Neurotoxic reactive astrocytes induce cell death via saturated lipids. Nature 599(7883):102\u2013107. https:\/\/doi.org\/10.1038\/s41586-021-03960-y","journal-title":"Nature"},{"key":"10199_CR38","doi-asserted-by":"publisher","first-page":"707","DOI":"10.3233\/JAD-160420","volume":"54","author":"S Hakobyan","year":"2016","unstructured":"Hakobyan S, Harding K, Aiyaz M et al (2016) Complement biomarkers as predictors of disease progression in Alzheimer\u2019s disease. J Alzheimers Dis 54:707\u2013716. https:\/\/doi.org\/10.3233\/JAD-160420","journal-title":"J Alzheimers Dis"},{"key":"10199_CR39","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.3390\/jcm10122580","volume":"10","author":"OA Halawa","year":"2021","unstructured":"Halawa OA, Lin JB, Miller JW, Vavvas DG (2021) A review of completed and ongoing complement inhibitor trials for geographic atrophy secondary to age-related macular degeneration. J Clin Med 10:2580. https:\/\/doi.org\/10.3390\/jcm10122580","journal-title":"J Clin Med"},{"key":"10199_CR40","doi-asserted-by":"publisher","unstructured":"Hallam TM, Gardenal E, McBlane F Ocular biomarker profiling after complement factor I gene therapy in geographic atrophy secondary to age-related macular degeneration eLife 13:RP99806., Hao J, Kwapong WR, Shen T et al (2025) (2024) Early detection of dementia through retinal imaging and trustworthy AI. NPJ Digit Med 7:294. https:\/\/doi.org\/10.1038\/s41746-024-01292-5","DOI":"10.1038\/s41746-024-01292-5"},{"key":"10199_CR41","doi-asserted-by":"publisher","DOI":"10.3389\/fddev.2024.1360302","volume":"4","author":"AS Haqqani","year":"2024","unstructured":"Haqqani AS, B\u00e9langer K, Stanimirovic DB (2024) Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria. Front Drug Deliv 4:1360302. https:\/\/doi.org\/10.3389\/fddev.2024.1360302","journal-title":"Front Drug Deliv"},{"issue":"19","key":"10199_CR42","doi-asserted-by":"publisher","first-page":"E3839","DOI":"10.1073\/pnas.1608769114","volume":"114","author":"JM Harder","year":"2017","unstructured":"Harder JM, Braine CE, Williams PA (2017) Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective. Proc Natl Acad Sci U S A 114(19):E3839\u2013E3848. https:\/\/doi.org\/10.1073\/pnas.1608769114","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10199_CR43","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.it.2012.06.001","volume":"33","author":"CL Harris","year":"2012","unstructured":"Harris CL, Heurich M, Cordoba S, Morgan BP (2012) The complotype: dictating risk for inflammation and infection. Trends Immunol 33:513\u2013521. https:\/\/doi.org\/10.1016\/j.it.2012.06.001","journal-title":"Trends Immunol"},{"key":"10199_CR44","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1016\/j.ophtha.2024.06.013","volume":"131","author":"JS Heier","year":"2024","unstructured":"Heier JS, Cohen MN, Chao DL et al (2024) Phase 1 study of JNJ-81201887 gene therapy in geographic atrophy secondary to age-related macular degeneration. Ophthalmology 131:1377\u20131388. https:\/\/doi.org\/10.1016\/j.ophtha.2024.06.013","journal-title":"Ophthalmology"},{"key":"10199_CR45","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1161\/STROKEAHA.112.660340","volume":"43","author":"N Heydenreich","year":"2012","unstructured":"Heydenreich N, Nolte MW, G\u00f6b E et al (2012) C1-inhibitor protects from brain ischemia-reperfusion injury by combined antiinflammatory and antithrombotic mechanisms. Stroke 43:2457\u20132467. https:\/\/doi.org\/10.1161\/STROKEAHA.112.660340","journal-title":"Stroke"},{"key":"10199_CR46","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.imbio.2015.04.005","volume":"221","author":"VM Holers","year":"2016","unstructured":"Holers VM (2016) Targeting mechanisms at sites of complement activation for imaging and therapy. Immunobiology 221:726\u2013732. https:\/\/doi.org\/10.1016\/j.imbio.2015.04.005","journal-title":"Immunobiology"},{"key":"10199_CR47","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1001\/jamaophthalmol.2018.1544","volume":"136","author":"FG Holz","year":"2018","unstructured":"Holz FG, Sadda SR, Busbee B et al (2018) Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: chroma and spectri phase 3 randomized clinical trials. JAMA Ophthalmol 136:666\u2013677. https:\/\/doi.org\/10.1001\/jamaophthalmol.2018.1544","journal-title":"JAMA Ophthalmol"},{"key":"10199_CR48","doi-asserted-by":"publisher","DOI":"10.1002\/alz.076151","volume":"19","author":"D Hondius","year":"2023","unstructured":"Hondius D, Veerhuis R, Li KW et al (2023) Full complement activation is associated with capillary cerebral amyloid angiopathy in Alzheimer\u2019s disease. Alzheimers Dement 19:e076151. https:\/\/doi.org\/10.1002\/alz.076151","journal-title":"Alzheimers Dement"},{"key":"10199_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39693-x","volume":"14","author":"M Hu","year":"2023","unstructured":"Hu M, Li T, Ma X et al (2023) Macrophage lineage cells-derived migrasomes activate complement-dependent blood-brain barrier damage in cerebral amyloid angiopathy mouse model. Nat Commun 14:3945. https:\/\/doi.org\/10.1038\/s41467-023-39693-x","journal-title":"Nat Commun"},{"key":"10199_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-016-0277-8","volume":"4","author":"WT Hu","year":"2016","unstructured":"Hu WT, Watts KD, Tailor P et al (2016) CSF complement 3 and factor H are staging biomarkers in Alzheimer\u2019s disease. Acta Neuropathol Commun 4:14. https:\/\/doi.org\/10.1186\/s40478-016-0277-8","journal-title":"Acta Neuropathol Commun"},{"key":"10199_CR51","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00278","volume":"11","author":"S Inafuku","year":"2018","unstructured":"Inafuku S, Klokman G, Connor KM (2018) The alternative complement system mediates cell death in retinal ischemia reperfusion injury. Front Mol Neurosci 11:278. https:\/\/doi.org\/10.3389\/fnmol.2018.00278","journal-title":"Front Mol Neurosci"},{"key":"10199_CR52","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1096\/fj.09-138834","volume":"24","author":"A Jacob","year":"2010","unstructured":"Jacob A, Hack B, Chiang E et al (2010) C5a alters blood-brain barrier integrity in experimental lupus. FASEB J 24:1682\u20131688. https:\/\/doi.org\/10.1096\/fj.09-138834","journal-title":"FASEB J"},{"key":"10199_CR53","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.ophtha.2020.08.027","volume":"128","author":"GJ Jaffe","year":"2021","unstructured":"Jaffe GJ, Westby K, Csaky KG et al (2021) C5 inhibitor Avacincaptad Pegol for geographic atrophy due to Age-Related macular degeneration: A randomized pivotal phase 2\/3 trial. Ophthalmology 128:576\u2013586. https:\/\/doi.org\/10.1016\/j.ophtha.2020.08.027","journal-title":"Ophthalmology"},{"key":"10199_CR54","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1016\/j.molimm.2011.07.012","volume":"48","author":"P Jha","year":"2011","unstructured":"Jha P, Banda H, Tytarenko R et al (2011) Complement mediated apoptosis leads to the loss of retinal ganglion cells in animal model of glaucoma. Mol Immunol 48:2151\u20132158. https:\/\/doi.org\/10.1016\/j.molimm.2011.07.012","journal-title":"Mol Immunol"},{"key":"10199_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0278-0","volume":"13","author":"H Jiao","year":"2018","unstructured":"Jiao H, Rutar M, Fernando N et al (2018) Subretinal macrophages produce classical complement activator C1q leading to the progression of focal retinal degeneration. Mol Neurodegener 13:45. https:\/\/doi.org\/10.1186\/s13024-018-0278-0","journal-title":"Mol Neurodegener"},{"key":"10199_CR56","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1613281","volume":"16","author":"K Jin","year":"2025","unstructured":"Jin K, Lizrova Preiningerova J, Grzybowski A (2025) Editorial: retina imaging in neurodegenerative disorders. Front Neurol 16:1613281. https:\/\/doi.org\/10.3389\/fneur.2025.1613281","journal-title":"Front Neurol"},{"key":"10199_CR57","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25557-8","volume":"8","author":"KJ Katschke","year":"2018","unstructured":"Katschke KJ, Xi H, Cox C et al (2018) Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy. Sci Rep 8:7348. https:\/\/doi.org\/10.1038\/s41598-018-25557-8","journal-title":"Sci Rep"},{"key":"10199_CR58","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1016\/S0140-6736(23)01583-0","volume":"402","author":"AM Khanani","year":"2023","unstructured":"Khanani AM, Patel SS, Staurenghi G et al (2023) Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial. Lancet 402:1449\u20131458. https:\/\/doi.org\/10.1016\/S0140-6736(23)01583-0","journal-title":"Lancet"},{"key":"10199_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57108-x","volume":"16","author":"N Khoury","year":"2025","unstructured":"Khoury N, Pizzo ME, Discenza CB et al (2025) Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution. Nat Commun 16:1822. https:\/\/doi.org\/10.1038\/s41467-025-57108-x","journal-title":"Nat Commun"},{"key":"10199_CR60","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93621","volume":"2","author":"Y Koronyo","year":"2017","unstructured":"Koronyo Y, Biggs D, Barron E et al (2017) Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer\u2019s disease. JCI Insight 2:e93621. https:\/\/doi.org\/10.1172\/jci.insight.93621","journal-title":"JCI Insight"},{"issue":"Suppl 1","key":"10199_CR61","doi-asserted-by":"publisher","first-page":"S204","DOI":"10.1016\/j.neuroimage.2010.06.020","volume":"54","author":"M Koronyo-Hamaoui","year":"2011","unstructured":"Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV et al (2011) Identification of amyloid plaques in retinas from alzheimer\u2019s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. NeuroImage 54(Suppl 1):S204\u2013217. https:\/\/doi.org\/10.1016\/j.neuroimage.2010.06.020","journal-title":"NeuroImage"},{"key":"10199_CR62","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1038\/ng.439","volume":"41","author":"J-C Lambert","year":"2009","unstructured":"Lambert J-C, Heath S, Even G et al (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer\u2019s disease. Nat Genet 41:1094\u20131099. https:\/\/doi.org\/10.1038\/ng.439","journal-title":"Nat Genet"},{"key":"10199_CR63","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1097\/WAD.0000000000000669","volume":"39","author":"C Leal-Bernal","year":"2025","unstructured":"Leal-Bernal C, Noriega- Ram\u00edrez S, \u00c1lvarez-Mart\u00ednez JV et al (2025) Retinal and vascular findings in optical coherence tomography in healthy cognitive patients with Alzheimer disease biomarkers: a systematic review and meta-analysis. Alzheimer Dis Assoc Disord 39:140. https:\/\/doi.org\/10.1097\/WAD.0000000000000669","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"10199_CR64","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-023-01377-5","volume":"16","author":"M Li","year":"2024","unstructured":"Li M, Ma Y-H, Guo Y et al (2024) Associations of cerebrospinal fluid complement proteins with Alzheimer\u2019s pathology, cognition, and brain structure in non-dementia elderly. Alzheimers Res Ther 16:12. https:\/\/doi.org\/10.1186\/s13195-023-01377-5","journal-title":"Alzheimers Res Ther"},{"key":"10199_CR65","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nrneurol.2012.227","volume":"9","author":"A London","year":"2013","unstructured":"London A, Benhar I, Schwartz M (2013) The retina as a window to the brain\u2014from eye research to CNS disorders. Nat Rev Neurol 9:44\u201353. https:\/\/doi.org\/10.1038\/nrneurol.2012.227","journal-title":"Nat Rev Neurol"},{"key":"10199_CR66","doi-asserted-by":"publisher","first-page":"8378","DOI":"10.1073\/pnas.92.18.8378","volume":"92","author":"C Lozada","year":"1995","unstructured":"Lozada C, Levin RI, Huie M et al (1995) Identification of C1q as the heat-labile serum cofactor required for immune complexes to stimulate endothelial expression of the adhesion molecules E-selectin and intercellular and vascular cell adhesion molecules 1. Proc Natl Acad Sci 92:8378\u20138382. https:\/\/doi.org\/10.1073\/pnas.92.18.8378","journal-title":"Proc Natl Acad Sci"},{"key":"10199_CR67","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/imm.12489","volume":"146","author":"SD Mahajan","year":"2015","unstructured":"Mahajan SD, Parikh NU, Woodruff TM et al (2015) C5a alters blood\u2013brain barrier integrity in a human in vitro model of systemic lupus erythematosus. Immunology 146:130\u2013143. https:\/\/doi.org\/10.1111\/imm.12489","journal-title":"Immunology"},{"key":"10199_CR68","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.11.39","volume":"61","author":"N Mandava","year":"2020","unstructured":"Mandava N, Tirado-Gonzalez V, Geiger MD et al (2020) Complement activation in the vitreous of patients with proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci 61:39. https:\/\/doi.org\/10.1167\/iovs.61.11.39","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10199_CR69","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1159\/000486091","volume":"44","author":"K Matsuo","year":"2017","unstructured":"Matsuo K, Shindo A, Niwa A et al (2017) Complement activation in capillary cerebral amyloid angiopathy. Dement Geriatr Cogn Disord 44:343\u2013353. https:\/\/doi.org\/10.1159\/000486091","journal-title":"Dement Geriatr Cogn Disord"},{"key":"10199_CR70","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1016\/j.jalz.2019.03.007","volume":"15","author":"AR Morgan","year":"2019","unstructured":"Morgan AR, Touchard S, Leckey C et al (2019) Inflammatory biomarkers in Alzheimer\u2019s disease plasma. Alzheimers Dement 15:776\u2013787. https:\/\/doi.org\/10.1016\/j.jalz.2019.03.007","journal-title":"Alzheimers Dement"},{"key":"10199_CR71","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.ymthe.2020.09.039","volume":"29","author":"T Okuyama","year":"2021","unstructured":"Okuyama T, Eto Y, Sakai N et al (2021) A phase 2\/3 trial of Pabinafusp alfa, IDS fused with anti-human transferrin receptor antibody, targeting neurodegeneration in MPS-II. Mol Ther 29:671\u2013679. https:\/\/doi.org\/10.1016\/j.ymthe.2020.09.039","journal-title":"Mol Ther"},{"key":"10199_CR72","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.59058","volume":"8","author":"S Paganoni","year":"2025","unstructured":"Paganoni S, Fournier CN, Macklin EA et al (2025) Efficacy and safety of Zilucoplan in amyotrophic lateral sclerosis: a randomized clinical trial. JAMA Netw Open 8:e2459058. https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.59058","journal-title":"JAMA Netw Open"},{"key":"10199_CR73","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00373","volume":"11","author":"WM Pardridge","year":"2020","unstructured":"Pardridge WM (2020) Blood-brain barrier and delivery of protein and gene therapeutics to brain. Front Aging Neurosci 11:373. https:\/\/doi.org\/10.3389\/fnagi.2019.00373","journal-title":"Front Aging Neurosci"},{"key":"10199_CR74","doi-asserted-by":"publisher","DOI":"10.1038\/srep26568","volume":"6","author":"CC Paun","year":"2016","unstructured":"Paun CC, Lechanteur YTE, Groenewoud JMM et al (2016) A novel complotype combination associates with age-related macular degeneration and high complement activation levels in vivo. Sci Rep 6:26568. https:\/\/doi.org\/10.1038\/srep26568","journal-title":"Sci Rep"},{"issue":"1","key":"10199_CR75","doi-asserted-by":"publisher","first-page":"100980","DOI":"10.1016\/j.xops.2025.100980","volume":"6","author":"S Rathi","year":"2025","unstructured":"Rathi S, Didangelos A, Pisarenka S et al (2025) CTx001 for geographic atrophy: A gene therapy expressing Soluble, truncated complement receptor 1 (Mini-CR1). Ophthalmol Sci 6(1):100980. https:\/\/doi.org\/10.1016\/j.xops.2025.100980","journal-title":"Ophthalmol Sci"},{"issue":"10","key":"10199_CR76","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.62.10.18","volume":"62","author":"B Rinsky","year":"2021","unstructured":"Rinsky B, Beykin G, Grunin M et al (2021) Analysis of the aqueous humor proteome in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci 62(10):18. https:\/\/doi.org\/10.1167\/iovs.62.10.18","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10199_CR77","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.survophthal.2023.02.004","volume":"68","author":"M Rispoli","year":"2023","unstructured":"Rispoli M, Cennamo G, Antonio LD et al (2023) Practical guidance for imaging biomarkers in exudative age-related macular degeneration. Surv Ophthalmol 68:615\u2013627. https:\/\/doi.org\/10.1016\/j.survophthal.2023.02.004","journal-title":"Surv Ophthalmol"},{"issue":"14","key":"10199_CR78","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1056\/NEJMoa054481","volume":"355","author":"PJ Rosenfeld","year":"2006","unstructured":"Rosenfeld PJ, Brown DM, Heier JS et al (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355(14):1419\u201331. https:\/\/doi.org\/10.1056\/NEJMoa054481","journal-title":"N Engl J Med"},{"key":"10199_CR79","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1002\/ana.24487","volume":"78","author":"S Saidha","year":"2015","unstructured":"Saidha S, Al-Louzi O, Ratchford JN et al (2015) Optical coherence tomography reflects brain atrophy in multiple sclerosis: a four-year study. Ann Neurol 78:801\u2013813. https:\/\/doi.org\/10.1002\/ana.24487","journal-title":"Ann Neurol"},{"key":"10199_CR80","doi-asserted-by":"publisher","first-page":"7940","DOI":"10.1002\/alz.14271","volume":"20","author":"C Sandoval","year":"2024","unstructured":"Sandoval C, Lee J, Toth B et al (2024) CSF complement proteins are elevated in prodromal to moderate Alzheimer\u2019s disease patients and are not altered by the anti-tau antibody semorinemab. Alzheimers Dement 20:7940\u20137953. https:\/\/doi.org\/10.1002\/alz.14271","journal-title":"Alzheimers Dement"},{"key":"10199_CR81","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/eye.2016.328","volume":"31","author":"T Schick","year":"2017","unstructured":"Schick T, Steinhauer M, Aslanidis A et al (2017) Local complement activation in aqueous humor in patients with age-related macular degeneration. Eye Lond 31:810\u2013813. https:\/\/doi.org\/10.1038\/eye.2016.328","journal-title":"Eye Lond"},{"key":"10199_CR82","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.molimm.2019.11.007.","volume":"118","author":"KT Simmons","year":"2020","unstructured":"Simmons KT, Mazzilli JL, Mueller-Ortiz SL et al (2020) Complement receptor 1 (CR1\/CD35)-expressing retinal pigment epithelial cells as a potential therapy for age-related macular degeneration. Mol Immunol 118:91\u201398. https:\/\/doi.org\/10.1016\/j.molimm.2019.11.007.","journal-title":"Mol Immunol"},{"key":"10199_CR83","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1167\/iovs.05-0830","volume":"47","author":"K Stasi","year":"2006","unstructured":"Stasi K, Nagel D, Yang X et al (2006) Complement component 1Q (C1Q) upregulation in retina of murine, primate, and human glaucomatous eyes. Invest Ophthalmol Vis Sci 47:1024\u20131029. https:\/\/doi.org\/10.1167\/iovs.05-0830","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10199_CR84","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","volume":"131","author":"B Stevens","year":"2007","unstructured":"Stevens B, Allen NJ, Vazquez LE et al (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131:1164\u20131178. https:\/\/doi.org\/10.1016\/j.cell.2007.10.036","journal-title":"Cell"},{"key":"10199_CR85","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.nbd.2004.11.001","volume":"19","author":"C Storini","year":"2005","unstructured":"Storini C, Rossi E, Marrella V et al (2005) C1-inhibitor protects against brain ischemia\u2013reperfusion injury via inhibition of cell recruitment and inflammation. Neurobiol Dis 19:10\u201317. https:\/\/doi.org\/10.1016\/j.nbd.2004.11.001","journal-title":"Neurobiol Dis"},{"key":"10199_CR86","doi-asserted-by":"publisher","first-page":"100290","DOI":"10.1016\/j.xops.2023.100290","volume":"3","author":"Y Sun","year":"2023","unstructured":"Sun Y, Wirta D, Murahashi W et al (2023) Safety and target engagement of complement C1q inhibitor ANX007 in neurodegenerative eye disease: results from phase I studies in glaucoma. Ophthalmol Sci 3:100290. https:\/\/doi.org\/10.1016\/j.xops.2023.100290","journal-title":"Ophthalmol Sci"},{"key":"10199_CR87","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131754","volume":"12","author":"SJ Tabor","year":"2023","unstructured":"Tabor SJ, Yuda K, Deck J et al (2023) Retinal injury activates complement expression in M\u00fcller cells leading to neuroinflammation and photoreceptor cell death. Cells 12:1754. https:\/\/doi.org\/10.3390\/cells12131754","journal-title":"Cells"},{"key":"10199_CR88","doi-asserted-by":"publisher","first-page":"5071","DOI":"10.1167\/iovs.10-5289","volume":"51","author":"G Tezel","year":"2010","unstructured":"Tezel G, Yang X, Luo C et al (2010) Oxidative stress and the regulation of complement activation in human glaucoma. Invest Ophthalmol Vis Sci 51:5071\u20135082. https:\/\/doi.org\/10.1167\/iovs.10-5289","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10199_CR89","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028527","volume":"6","author":"M Thambisetty","year":"2011","unstructured":"Thambisetty M, Simmons A, Hye A et al (2011) Plasma biomarkers of brain atrophy in Alzheimer\u2019s disease. PLOS ONE 6:e28527. https:\/\/doi.org\/10.1371\/journal.pone.0028527","journal-title":"PLOS ONE"},{"key":"10199_CR90","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1007\/978-1-4614-4118-2_19","volume":"735","author":"JM Thurman","year":"2013","unstructured":"Thurman JM, Rohrer B (2013) Noninvasive detection of complement activation through radiologic imaging. Adv Exp Med Biol 735:271\u2013282. https:\/\/doi.org\/10.1007\/978-1-4614-4118-2_19","journal-title":"Adv Exp Med Biol"},{"key":"10199_CR91","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1161\/01.cir.101.4.352","volume":"101","author":"C Urbich","year":"2000","unstructured":"Urbich C, Fritzenwanger M, Zeiher AM, Dimmeler S (2000) Laminar shear stress upregulates the complement-inhibitory protein clusterin : a novel potent defense mechanism against complement-induced endothelial cell activation. Circulation 101:352\u2013355. https:\/\/doi.org\/10.1161\/01.cir.101.4.352","journal-title":"Circulation"},{"key":"10199_CR92","doi-asserted-by":"publisher","first-page":"34","DOI":"10.2174\/156720511794604589","volume":"8","author":"R Veerhuis","year":"2011","unstructured":"Veerhuis R (2011) Histological and direct evidence for the role of complement in the neuroinflammation of AD. Curr Alzheimer Res 8:34\u201358. https:\/\/doi.org\/10.2174\/156720511794604589","journal-title":"Curr Alzheimer Res"},{"key":"10199_CR93","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02850-6","volume":"20","author":"A Veteleanu","year":"2023","unstructured":"Veteleanu A, Stevenson-Hoare J, Keat S et al (2023) Alzheimer\u2019s disease-associated complement gene variants influence plasma complement protein levels. J Neuroinflammation 20:169. https:\/\/doi.org\/10.1186\/s12974-023-02850-6","journal-title":"J Neuroinflammation"},{"key":"10199_CR94","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41433-022-02056-9","volume":"37","author":"S Vujosevic","year":"2023","unstructured":"Vujosevic S, Parra MM, Hartnett ME et al (2023) Optical coherence tomography as retinal imaging biomarker of neuroinflammation\/neurodegeneration in systemic disorders in adults and children. Eye 37:203\u2013219. https:\/\/doi.org\/10.1038\/s41433-022-02056-9","journal-title":"Eye"},{"key":"10199_CR95","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116038","volume":"44","author":"RC Wells","year":"2025","unstructured":"Wells RC, Akkapeddi P, Chan D et al (2025) Dual targeting of transferrin receptor and CD98hc enhances brain exposure of large molecules. Cell Rep 44:116038. https:\/\/doi.org\/10.1016\/j.celrep.2025.116038","journal-title":"Cell Rep"},{"key":"10199_CR96","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci14060601","volume":"14","author":"CD Whinnery","year":"2024","unstructured":"Whinnery CD, Nie Y, Boskovic DS et al (2024) CD59 protects primary human cerebrovascular smooth muscle cells from cytolytic membrane attack complex. Brain Sci 14:601. https:\/\/doi.org\/10.3390\/brainsci14060601","journal-title":"Brain Sci"},{"key":"10199_CR97","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-016-0091-6","volume":"11","author":"PA Williams","year":"2016","unstructured":"Williams PA, Tribble JR, Pepper KW et al (2016) Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma. Mol Neurodegener 11:26. https:\/\/doi.org\/10.1186\/s13024-016-0091-6","journal-title":"Mol Neurodegener"},{"key":"10199_CR98","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0485-y","volume":"13","author":"F Wu","year":"2016","unstructured":"Wu F, Zou Q, Ding X et al (2016) Complement component C3a plays a critical role in endothelial activation and leukocyte recruitment into the brain. J Neuroinflammation 13:23. https:\/\/doi.org\/10.1186\/s12974-016-0485-y","journal-title":"J Neuroinflammation"},{"key":"10199_CR99","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1016\/j.celrep.2019.07.060","volume":"28","author":"T Wu","year":"2019","unstructured":"Wu T, Dejanovic B, Gandham VD et al (2019) Complement C3 is activated in human AD brain and is required for neurodegeneration in mouse models of amyloidosis and tauopathy. Cell Rep 28:2111\u20132123e6. https:\/\/doi.org\/10.1016\/j.celrep.2019.07.060","journal-title":"Cell Rep"},{"key":"10199_CR100","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.ajo.2025.04.016","volume":"276","author":"CC Wykoff","year":"2025","unstructured":"Wykoff CC, Holz FG, Chiang A et al (2025) Pegcetacoplan treatment for geographic atrophy in age-related macular degeneration over 36 months: data from OAKS, DERBY, and GALE. Am J Ophthalmol 276:350\u2013364. https:\/\/doi.org\/10.1016\/j.ajo.2025.04.016","journal-title":"Am J Ophthalmol"},{"key":"10199_CR101","doi-asserted-by":"publisher","first-page":"6271","DOI":"10.3390\/ijms26136271","volume":"26","author":"H-M Yang","year":"2025","unstructured":"Yang H-M (2025) Recent advances in antibody therapy for Alzheimer\u2019s disease: focus on bispecific antibodies. Int J Mol Sci 26:6271. https:\/\/doi.org\/10.3390\/ijms26136271","journal-title":"Int J Mol Sci"},{"key":"10199_CR102","doi-asserted-by":"publisher","DOI":"10.1186\/s40942-022-00431-y","volume":"8","author":"T Yednock","year":"2022","unstructured":"Yednock T, Fong DS, Lad EM (2022) C1q and the classical complement cascade in geographic atrophy secondary to age-related macular degeneration. Int J Retina Vitreous 8:79. https:\/\/doi.org\/10.1186\/s40942-022-00431-y","journal-title":"Int J Retina Vitreous"},{"key":"10199_CR103","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.bbi.2024.03.017","volume":"118","author":"WM Zelek","year":"2024","unstructured":"Zelek WM, Bevan RJ, Morgan BP (2024) Targeting terminal pathway reduces brain complement activation, amyloid load and synapse loss, and improves cognition in a mouse model of dementia. Brain Behav Immun 118:355\u2013363. https:\/\/doi.org\/10.1016\/j.bbi.2024.03.017","journal-title":"Brain Behav Immun"},{"key":"10199_CR104","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1093\/brain\/awae278","volume":"148","author":"WM Zelek","year":"2025","unstructured":"Zelek WM, Bevan RJ, Nimmo J et al (2025) Brain-penetrant complement inhibition mitigates neurodegeneration in an Alzheimer\u2019s disease mouse model. Brain 148:941\u2013954. https:\/\/doi.org\/10.1093\/brain\/awae278","journal-title":"Brain"},{"key":"10199_CR105","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.tips.2022.02.006","volume":"43","author":"WM Zelek","year":"2022","unstructured":"Zelek WM, Morgan BP (2022) Targeting complement in neurodegeneration: challenges, risks, and strategies. Trends Pharmacol Sci 43:615\u2013628. https:\/\/doi.org\/10.1016\/j.tips.2022.02.006","journal-title":"Trends Pharmacol Sci"},{"key":"10199_CR106","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2025.153089","volume":"230","author":"WM Zelek","year":"2025","unstructured":"Zelek WM, Tenner AJ (2025) Complement therapeutics in neurodegenerative diseases. Immunobiology 230:153089. https:\/\/doi.org\/10.1016\/j.imbio.2025.153089","journal-title":"Immunobiology"},{"key":"10199_CR107","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.molimm.2019.07.030","volume":"114","author":"WM Zelek","year":"2019","unstructured":"Zelek WM, Xie L, Morgan BP, Harris CL (2019) Compendium of current complement therapeutics. Mol Immunol 114:341\u2013352. https:\/\/doi.org\/10.1016\/j.molimm.2019.07.030","journal-title":"Mol Immunol"},{"key":"10199_CR108","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1038\/npp.2015.232","volume":"41","author":"D-F Zhang","year":"2016","unstructured":"Zhang D-F, Li J, Wu H et al (2016) CFH variants affect structural and functional brain changes and genetic risk of Alzheimer\u2019s disease. Neuropsychopharmacology 41:1034\u20131045. https:\/\/doi.org\/10.1038\/npp.2015.232","journal-title":"Neuropsychopharmacology"},{"key":"10199_CR109","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-021-00230-9","volume":"10","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Wang Y, Shi C et al (2021) Advances in retina imaging as potential biomarkers for early diagnosis of Alzheimer\u2019s disease. Transl Neurodegener 10:6. https:\/\/doi.org\/10.1186\/s40035-021-00230-9","journal-title":"Transl Neurodegener"}],"container-title":["Mammalian Genome"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00335-026-10199-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00335-026-10199-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00335-026-10199-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:02:27Z","timestamp":1781650947000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00335-026-10199-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":109,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["10199"],"URL":"https:\/\/doi.org\/10.1007\/s00335-026-10199-3","relation":{},"ISSN":["0938-8990","1432-1777"],"issn-type":[{"value":"0938-8990","type":"print"},{"value":"1432-1777","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"assertion":[{"value":"1 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised: The note in the article \u201cJacqui Nimmo, Matthew Bright, Nikoleta Daskoulidou and Wioleta Milena Zelek have contributed equally and also joint first authors to this work\u201d has been corrected to \u201cJacqui Nimmo and Matthew Bright are joint first authors who contributed equally. Nikoleta Daskoulidou and Wioleta Milena Zelek are joint senior and corresponding authors who contributed equally\u201d.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33"}}