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Long\u2010read sequencing enables analysis of \u201cdark regions\u201d that are difficult to study via traditional sequencing methodologies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Using nanopore whole\u2010genome DNA sequencing of\n                      <jats:italic>post mortem<\/jats:italic>\n                      brain from early\u2010 and late\u2010 stage Alzheimer's disease cases and controls, we analyzed retrotransposition, non\u2010allelic homologous recombination (NAHR), structural variation, and DNA methylation within repetitive regions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Retrotransposon insertions and NAHR were enriched in centromeric\/pericentromeric and ribosomal DNA (rDNA) in the aged brain. Putatively somatic AluY retrotransposon insertions trended upward in late\u2010stage disease. Enrichment of NAHR between repetitive regions and DNA demethylation were detected in early disease. Differential methylation of dark regions within specific Alzheimer's disease risk genes and repetitive elements occurred across disease stage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>This study provides the first long\u2010read analysis of repetitive elements in the aged human brain and identifies these regions as hotspots for genomic variation in Alzheimer's disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Long\u2010read sequencing enables analysis of \u201cdark\u201d regions Alzheimer's disease brains<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Somatic AluY retrotransposon insertions may be elevated in late\u2010stage disease<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Retrotransposon\u2010associated non\u2010allelic homologous recombination (NAHR) is enriched in repetitive regions in early disease<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>DNA demethylation within the centro\/pericentromere and ribosomal DNA (rDNA) occur across disease stage<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Dark regions of risk genes are differentially methylated across disease stage<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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