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In this <jats:italic>Correspondence<\/jats:italic>, we discuss three examples, microRNA 155 (miR155), TREM2, and INPP5D, in which <jats:italic>observed<\/jats:italic> results have been difficult to reconcile with <jats:italic>predicted<\/jats:italic> results based on precedent, because these six key endpoints do not reliably track together. The pathogenesis of AD involves multiple cell types and complex events that may change with disease stage. We propose that cell-type targeting and timing of intervention are responsible for the sometimes impossibility of predicting whether any prospective therapeutic intervention should aim at increasing or decreasing the level or activity of a particular molecular target.<\/jats:p>","DOI":"10.1186\/s12974-023-02895-7","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T11:02:44Z","timestamp":1695639764000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["miR155, TREM2, INPP5D: Disease stage and cell type are essential considerations when targeting clinical interventions based on mouse models of Alzheimer\u2019s amyloidopathy"],"prefix":"10.1186","volume":"20","author":[{"given":"Sam","family":"Gandy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle E.","family":"Ehrlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"issue":"1","key":"2895_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.gene.2012.12.009","volume":"532","author":"TS Elton","year":"2013","unstructured":"Elton TS, Selemon H, Elton SM, Parinandi NL. 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He has received research support in the past from Warner-Lambert, Pfizer, Baxter, and Avid. Dr Ehrlich has no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"214"}}