{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:07:33Z","timestamp":1790514453255,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["MC_PC_17112"],"award-info":[{"award-number":["MC_PC_17112"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The presence of complement activation products at sites of pathology in post-mortem Alzheimer\u2019s disease (AD) brains is well known. Recent evidence from genome-wide association studies (GWAS), combined with the demonstration that complement activation is pivotal in synapse loss in AD, strongly implicates complement in disease aetiology. Genetic variations in complement genes are widespread. While most variants individually have only minor effects on complement homeostasis, the combined effects of variants in multiple complement genes, referred to as the \u201ccomplotype\u201d, can have major effects. In some diseases, the complotype highlights specific parts of the complement pathway involved in disease, thereby pointing towards a mechanism; however, this is not the case with AD. Here we review the complement GWAS hits; CR1 encoding complement receptor 1 (CR1), CLU encoding clusterin, and a suggestive association of C1S encoding the enzyme C1s, and discuss difficulties in attributing the AD association in these genes to complement function. A better understanding of complement genetics in AD might facilitate predictive genetic screening tests and enable the development of simple diagnostic tools and guide the future use of anti-complement drugs, of which several are currently in development for central nervous system disorders.<\/jats:p>","DOI":"10.3390\/genes12121990","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T09:02:19Z","timestamp":1639558939000},"page":"1990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Genetic Insights into the Impact of Complement in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Megan","family":"Torvell","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK"},{"name":"Division of Infection and Immunity, Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7609-7529","authenticated-orcid":false,"given":"Sarah M.","family":"Carpanini","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK"},{"name":"Division of Infection and Immunity, Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikoleta","family":"Daskoulidou","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK"},{"name":"Division of Infection and Immunity, Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A. J.","family":"Byrne","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK"},{"name":"Division of Infection and Immunity, Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3885-1199","authenticated-orcid":false,"given":"Rebecca","family":"Sims","sequence":"additional","affiliation":[{"name":"Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4075-7676","authenticated-orcid":false,"given":"B. Paul","family":"Morgan","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Cardiff, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK"},{"name":"Division of Infection and Immunity, Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018). Towards a Dementia Plan: A WHO Guide, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a central mechanism in Alzheimer\u2019s disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimers Dement. N. 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