{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:28:09Z","timestamp":1772252889811,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Genetic discoveries related to Alzheimer\u2019s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. In the present study, 70 single-point mutations on the APP gene in a publicly available genetic dataset that included 2504 healthy individuals from 26 populations were scanned, and their distribution was analyzed. Furthermore, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations were detected in the worldwide dataset, with several of them being specific for a single individual, population, or macroarea. Patterns of segment sharing reflected recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementia.<\/jats:p>","DOI":"10.3390\/ijms232415871","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T02:54:21Z","timestamp":1670986461000},"page":"15871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rare Amyloid Precursor Protein Point Mutations Recapitulate Worldwide Migration and Admixture in Healthy Individuals: Implications for the Study of Neurodegeneration"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9626-8495","authenticated-orcid":false,"given":"Paolo","family":"Abondio","sequence":"first","affiliation":[{"name":"Laboratory of Ancient DNA, Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy"},{"name":"Laboratory of Molecular Anthropology and Center for Genome Biology, Department of Biological, Geological and Environmental Sciences, University of Bologna, Via Selmi 3, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1377-4489","authenticated-orcid":false,"given":"Francesco","family":"Bruno","sequence":"additional","affiliation":[{"name":"Regional Neurogenetic Center (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, Italy"},{"name":"Association for Neurogenetic Research (ARN), 88046 Lamezia Terme, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amalia Cecilia","family":"Bruni","sequence":"additional","affiliation":[{"name":"Regional Neurogenetic Center (CRN), Department of Primary Care, ASP Catanzaro, 88046 Lamezia Terme, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2105-2478","authenticated-orcid":false,"given":"Donata","family":"Luiselli","sequence":"additional","affiliation":[{"name":"Laboratory of Ancient DNA, Department of Cultural Heritage, University of Bologna, Via degli Ariani 1, 48121 Ravenna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.18388\/abp.2005_3454","article-title":"Molecular mechanisms initiating amyloid beta-fibril formation in Alzheimer\u2019s disease","volume":"52","author":"Kirkitadze","year":"2005","journal-title":"Acta Biochim. 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