New research points to malfunctioning tau, not amyloid-beta (Abeta) plaque, as the seminal event that spurs neuron death in disorders such as Alzheimer\u2019s disease. The finding, which dramatically alters the prevailing theory of Alzheimer\u2019s development, also explains why some people with plaque build-up in their brains don\u2019t have dementia.<\/p>\n
Neuronal death happens when tau, found inside neurons, fails to function. Tau\u2019s role is to provide a structure \u2014 like a train track \u2014inside brain neurons that allows the cells to clear accumulation of unwanted and toxic proteins.<\/p>\n
\u201cWhen tau is abnormal, these proteins, which include Abeta, accumulate inside the neurons,\u201d explains the study\u2019s senior investigator, Charbel E-H Moussa, MB, PhD, assistant professor of neuroscience at Georgetown University Medical Center. \u201cThe cells start to spit the proteins out, as best they can, into the extracellular space so that they cannot exert their toxic effects inside the cell. Because Abeta is \u2018sticky,\u2019 it clumps together into plaque,\u201d Moussa says.<\/p>\n
He says his study suggests the remaining Abeta inside the neuron (that isn\u2019t pushed out) destroys the cells, not the plaques that build up outside. \u201cWhen tau does not function, the cell cannot remove the garbage, which at that point includes Abeta as well as tangles of non-functioning tau, and the cell dies. The Abeta released from the dead neuron then sticks to the plaque that had been forming.\u201d<\/p>\n
Moussa\u2019s experiments in animal models also show less plaques accumulate outside the cell when tau is functioning; when tau was reintroduced into neurons that did not have it, plaques did not grow.<\/p>\n
Malfunctioning tau can occur due to errant genes or through aging. As individuals grow older, some tau can malfunction while enough normal tau remains to help clear the garbage. In these cases, the neurons don\u2019t die, he says. \u201cThat explains the confusing clinical observations of older people who have plaque build-up, but no dementia,\u201d Moussa says.<\/p>\n
Moussa has long sought a way to force neurons to clean up their garbage. In this study, he shows that nilotinib, a drug approved to treat cancer, can aid in that process. Nilotinib helps the neuron clear garbage, but requires some functional tau, he says.<\/p>\n
\u201cThis drug can work if there is a higher percentage of good to bad tau in the cell,\u201d Moussa says. \u201cThere are many diseases of dementia that have malfunctioning tau and no plaque accumulation, such as frontal temporal dementia linked to Parkinsonism,\u201d Moussa says. \u201cThe common culprit is tau, so a drug that helps tau do its job may help protect against progression of these diseases.\u201d\nGeorgetown University Medical Center<\/link>\n","protected":false},"excerpt":{"rendered":"
New research points to malfunctioning tau, not amyloid-beta (Abeta) plaque, as the seminal event that spurs neuron death in disorders such as Alzheimer\u2019s disease. The finding, which dramatically alters the prevailing theory of Alzheimer\u2019s development, also explains why some people with plaque build-up in their brains don\u2019t have dementia. Neuronal death happens when tau, found […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"class_list":["post-1516","post","type-post","status-publish","format-standard","hentry","category-e-news"],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1516"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=1516"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/1516\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=1516"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=1516"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=1516"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}