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Here, a retrospective look on the most prominent GWAS was performed, focusing on the quality of the diagnosis associated with the used data and databases. Different methods for AD diagnosis (or absence) carry different levels of accuracy and certainty applied to both subsets of cases and controls. Furthermore, the different phenotypes included in these databases were explored, as several incorporate other ageing comorbidities and might be encompassing many confounding agents as well. Age of the samples\u2019 donors and origin populations were also investigated as these could be biasing factors in posterior analyses. A tendency for looser diagnostic methods in more recent GWAS was observed, where greater datasets of individuals are analyzed, which may have been hampering the discovery of associated genetic variants. Specifically for AD, a diagnostic method conveying a clinical outcome may be distinct from the disease neuropathological assessment, since the first has a practical perspective that not necessarily needs a confirmation. Due to its properties and complex diagnosis, this work highlights the importance of the neuropathological confirmation of AD (or its absence) in the subjects considered for research purposes to avoid reaching statistically weak and\/or misleading conclusions that may trigger further studies with powerless groundwork.<\/jats:p>","DOI":"10.1177\/13872877251317543","type":"journal-article","created":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T23:49:21Z","timestamp":1739749761000},"page":"611-626","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Navigating the blurred boundary: Neuropathologic changes versus clinical symptoms in Alzheimer\u2019s disease, and its consequences for research in genetics"],"prefix":"10.1177","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3522-1631","authenticated-orcid":false,"given":"Catarina","family":"Xavier","sequence":"first","affiliation":[{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1903-4206","authenticated-orcid":false,"given":"N\u00e1dia","family":"Pinto","sequence":"additional","affiliation":[{"name":"i3S \u2014 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"IPATIMUP \u2014 Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal"},{"name":"CMUP \u2014 Centro de Matem\u00e1tica da Universidade do Porto, Porto, Portugal"}]}],"member":"179","published-online":{"date-parts":[[2025,2,16]]},"reference":[{"key":"e_1_3_5_2_2","unstructured":"Long S Benoist C Weidner W. 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