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Clinical research and genome-wide association studies have suggested a potential contribution of the endocytic pathway to AD, with an emphasis on common loci. However, the contribution of rare variants in this pathway to AD has not been thoroughly investigated. In this study, we focused on the effect of rare variants on AD by first applying a rare-variant gene-set burden analysis using genes in the endocytic pathway on over 3,000 individuals with European ancestry from three large whole-genome sequencing (WGS) studies. We identified significant associations of rare-variant burden within the endocytic pathway with AD, which were successfully replicated in independent datasets. We further demonstrated that this endocytic rare-variant enrichment is associated with neurofibrillary tangles (NFTs) and age-related phenotypes, increasing the risk of obtaining severer brain damage, earlier age-at-onset, and earlier age-of-death. Next, by aggregating rare variants within each gene, we sought to identify single endocytic genes associated with AD and NFTs. Careful examination using NFTs revealed one significantly associated gene, <jats:italic>ANKRD13D<\/jats:italic>. To identify functional associations, we integrated bulk RNA-Seq data from over 600 brain tissues and found two endocytic expression genes (eGenes), <jats:italic>HLA-A<\/jats:italic> and <jats:italic>SLC26A7<\/jats:italic>, that displayed significant influences on their gene expressions. Differential expressions between AD patients and controls of these three identified genes were further examined by incorporating scRNA-Seq data from 48 post-mortem brain samples and demonstrated distinct expression patterns across cell types. Taken together, our results demonstrated strong rare-variant effect in the endocytic pathway on AD risk and progression and functional effect of gene expression alteration in both bulk and single-cell resolution, which may bring more insight and serve as valuable resources for future AD genetic studies, clinical research, and therapeutic targeting.<\/jats:p>","DOI":"10.1371\/journal.pgen.1009772","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T17:33:21Z","timestamp":1631554401000},"page":"e1009772","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Rare variants in the endocytic pathway are associated with Alzheimer\u2019s disease, its related phenotypes, and functional 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Burana","year":"2016","journal-title":"J Biol Chem"},{"issue":"1","key":"pgen.1009772.ref120","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5498\/wjp.v1.i1.8","article-title":"Cerebrospinal fluid and blood biomarkers in Alzheimer\u2019s disease","volume":"1","author":"C Humpel","year":"2011","journal-title":"World J Psychiatry"},{"issue":"10","key":"pgen.1009772.ref121","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1001\/archneurol.2012.1282","article-title":"Blood-based protein biomarkers for diagnosis of Alzheimer disease","volume":"69","author":"JD Doecke","year":"2012","journal-title":"Arch Neurol"},{"issue":"1","key":"pgen.1009772.ref122","doi-asserted-by":"crossref","first-page":"e29868","DOI":"10.1371\/journal.pone.0029868","article-title":"Evaluation of a previously suggested plasma biomarker panel to identify Alzheimer\u2019s disease.","volume":"7","author":"M Bjorkqvist","year":"2012","journal-title":"PLoS One."},{"issue":"1","key":"pgen.1009772.ref123","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s40478-016-0387-3","article-title":"Epidermal growth factor prevents APOE4 and amyloid-beta-induced cognitive and cerebrovascular deficits in female mice","volume":"4","author":"R Thomas","year":"2016","journal-title":"Acta Neuropathol Commun"},{"issue":"11","key":"pgen.1009772.ref124","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1177\/0271678X16669956","article-title":"Epidermal growth factor prevents oligomeric amyloid-beta induced angiogenesis deficits in vitro","volume":"36","author":"KP Koster","year":"2016","journal-title":"J Cereb Blood Flow Metab"},{"key":"pgen.1009772.ref125","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.0105-2896.2005.00316.x","article-title":"Mechanisms of MHC class I-restricted antigen processing and cross-presentation","volume":"207","author":"P Cresswell","year":"2005","journal-title":"Immunol 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