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However, the consequences of CAA on blood\u2013brain barrier (BBB) integrity and the neurovascular unit (NVU) are still not well understood. Systematic search was conducted on PubMed using 12 targeted keywords related to CAA, BBB, and the NVU in combination with DS. Additional sources were identified and the research gap validated using Consensus and ChatGPT\u2010assisted literature screening. Individuals with DS are vulnerable to cerebrovascular conditions across their lifespan. Despite pronounced A\u03b2 pathology, CAA appears less frequent than in cases with microduplication of the\n                      <jats:italic>APP<\/jats:italic>\n                      locus, suggesting distinct vascular dynamics potentially influenced by chromosome 21 genes. Limited direct evidence on BBB integrity in DS highlights the need for mechanistic and longitudinal studies. DS offers a unique lens for exploring cerebrovascular resilience and CAA pathogenesis.\n                    <\/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>Down syndrome (DS) individuals overexpressing amyloid precursor protein (APP) are at risk for cerebral amyloid angiopathy (CAA) and lobar microbleeds.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            CAA is less severe in DS compared to APP microduplication (\n                            <jats:italic>APP<\/jats:italic>\n                            dup) cases.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Intracerebral hemorrhage (ICH) is less common in DS than in\n                            <jats:italic>APP<\/jats:italic>\n                            dup cases.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>DS may have protective mechanisms against CAA and ICH involving BBB function.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Few longitudinal studies examine BBB permeability in DS across the lifespan.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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