On Thursday, May 14, 2020 Dr. Liz Head presented her work on Alzheimer\u2019s disease in Down Syndrome.<\/p>\n
Why is it useful to study the pathology of AD that is associated with Down syndrome?\u00a0 <\/em><\/p>\n Down syndrome occurs when an individual has a full or partial extra copy of chromosome 21.\u00a0 This same chromosome carries the gene for the amyloid precursor protein (APP), as well as genes associated with the accumulation of hyper-phosphorylated tau (p-tau) and synaptogenesis.\u00a0 Those with Down syndrome express 1.5 times the usual amount of APP, which translates into increased levels at amyloid beta (A\u03b2), which becomes apparent at younger ages.<\/p>\n Dr. Head cited previous studies which demonstrated that almost all adults with Down Syndrome over the age of 40 have AD pathology, including plaques and tangles.\u00a0 She noted a dramatic spike in pathology between ages 30 and 40 in those with Down Syndrome, even though symptoms of AD dementia may not emerge until decades later.<\/p>\n Her group aimed to test the hypothesis that in those with Down syndrome the frontal cortex are especially vulnerable to aging and AD.\u00a0 This does seem to be the case.\u00a0 In preserved brain sections they found a loss of connectivity (i.e. white matter integrity) in this region starting by 35 years, sometimes earlier.<\/p>\n This can be caused by cerebrovascular problems, such as atherosclerosis or hypertension which prevent adequate blood flow to the brain. \u00a0But individuals with Down syndrome rarely have atherosclerosis or hypertension.<\/p>\n Dr. Head\u2019s group wondered about a different type of vascular damage, cerebral amyloid angiopathy (CAA).<\/p>\n Cerebral amyloid angiopathy occurs when amyloid proteins build up on the walls of the arteries, impeding blood flow, disrupting the blood brain barrier, and increasing the risk for dementia.<\/p>\n Indeed, her lab group found evidence of significant CAA \u2013 including high levels of A\u03b242<\/sub> and A\u03b240<\/sub> around brain blood vessels in these individuals.<\/p>\n CCA can result in microhemorrhages, or small bleeds in the brain.\u00a0 And Dr. Head found evidence for a greatly increased prevalence of microhemorrhages by staining of archived brain sections and examining non-invasive MRI scans of individuals.<\/p>\n Microhemorrhages can led to physical damage of the brain, as well as inflammation and an activation of immune responses.<\/p>\n This was apparent when gene expression was quantified by RT-PCR in frontal cortex samples.\u00a0 Samples of FC tissue from AD patients showed increases in inflammation \u2013 including increased expression of IL-6, TNF\u03b1, IL-12, and TFG\u03b2.<\/p>\n Similar tissue samples from individuals with Down syndrome exhibited markers of inflammation even before AD pathology set in.\u00a0 The combination of DS and AD made the situation worse \u2013 not only did these individuals show the highest inflammatory markers but there was also evidence of a chronic immune response as well.<\/p>\n This immune response was clear in microglia observed in the posterior cingulate cortex.<\/p>\n The posterior cingulate cortex (PCC) is buried deep within the brain.\u00a0 It has diverse functions, acting as a sort of connection center in the brain.\u00a0 It is highly active and demands great blood flow than most other areas of the brain.<\/p>\n Microglia are a type of glial cell.\u00a0 They are the primary active immune defense of the central nervous system.\u00a0 Ameboid microglia wander through the central nervous system, looking for trouble.\u00a0 Ramified or \u201cresting\u201d microglia are held in reserve.\u00a0 They are less active but can respond to damage and infection, changing their shape and behavior (becoming \u201chypertropic\u201d or \u201cdystropic\u201d) to defend brain tissues.<\/p>\n Dr. Head found that normal aging results in fewer ramified or \u201cresting\u201d microglia by more hyper- and dys-tropic cells in both white matter and grey matter of the PCC.\u00a0 This trend was increased in AD and greatly increased in samples from those with both Down syndrome and Alzheimer\u2019s Disease.\u00a0 This lends support to her previous gene expression data.<\/p>\n Together, these results suggest that A\u03b2 accumulations, CCA, and inflammation \/ immune responses follow a time course and are good targets for intervention.<\/p>\n","protected":false},"excerpt":{"rendered":" Dr. Elizabeth Head, Professor, University of California Irvine Alzheimer\u2019s disease in Down syndrome: Link between Cerebrovascular pathology On Thursday, May 14, 2020 Dr. Liz Head presented her work…<\/p>\n","protected":false},"author":1263,"featured_media":1148,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1147","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"_links":{"self":[{"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/posts\/1147","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/users\/1263"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/comments?post=1147"}],"version-history":[{"count":1,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/posts\/1147\/revisions"}],"predecessor-version":[{"id":1352,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/posts\/1147\/revisions\/1352"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/media\/1148"}],"wp:attachment":[{"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/media?parent=1147"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/categories?post=1147"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.dickinson.edu\/arnoldt\/wp-json\/wp\/v2\/tags?post=1147"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}