{"id":596,"date":"2017-01-06T03:28:10","date_gmt":"2017-01-06T08:28:10","guid":{"rendered":"http:\/\/www.bocsci.com\/blog\/?p=596"},"modified":"2018-01-03T22:50:11","modified_gmt":"2018-01-04T03:50:11","slug":"amyoid-b","status":"publish","type":"post","link":"https:\/\/www.bocsci.com\/blog\/amyoid-b\/","title":{"rendered":"Amyoid-\u03b2"},"content":{"rendered":"

The clinical\u00a0symptoms and signs of Alzheimer’s disease<\/a> (AD)\u00a0result from abnormalities associated with neuronal\u00a0dysfunction and cell death in specific brain regions which are important in memory and\u00a0cognitive functions. Damaged circuits include the basal forebrain cholinergic system,\u00a0amygdala, hippocampus, entorhinal and limbic cortex, and specific regions of neocortex. Major\u00a0pathological hallmarks of AD are extracellular amyloid plaques and intracelluar\u00a0neurofibrillary tangles. Neurofibrillary tangles are composed of phosphorylated and\u00a0aggregated forms of tau which is assembled into the paired helical filaments, and amyloid\u00a0plaques are composed of A\u03b2\u00a0peptides existing in the extracellular space in \u03b2-pleated\u00a0sheet conformations.<\/p>\n

Amyiold plaques are critical for the diagnosis of AD and the major component of\u00a0amyloid plauqes is amyoid-\u03b2\u00a0(A\u03b2) peptide. Aggregation of the amyloid-\u03b2\u00a0<\/a>(A\u03b2) peptide in the extracellular space of the brain is\u00a0critical in the pathogenesis of Alzheimer’s disease (AD). A\u03b2\u00a0is produced by neurons and\u00a0released into the brain interstitial fluid (ISF), a process regulated by synaptic activity.\u00a0The process of A\u03b2\u00a0aggregation is believed to be concentration dependent in the\u00a0extracellular space. A\u03b2\u00a0is a peptide fragment, principally 40 or 42\u00a0amino acids long, that is proteolytically cleaved from a large precursor polypeptide,\u00a0amyloid-\u03b2\u00a0precursor protein (APP). Once generated, A\u03b2\u00a0can exist in a soluble monomeric\u00a0state or potentially in oligomeric forms or fibrils. There is strong evidence that A\u03b2\u00a0may\u00a0play a central role in AD. First, all patients with AD accumulate deposits\u00a0of A\u03b242 and A\u03b240 in vulnerable brain regions. Second, most autosomal dominant\u00a0mutations in APP and in the presenilins alter APP processing which results in more\u00a0production of A\u03b242. Third, some APP mutations are in the A\u03b2 region and cause altered fibrillogenesis or clearance of A\u03b2\u00a0without affecting APP\u00a0processing. Down syndrome individuals who are trisomic for APP\u00a0as well as other genes develop AD pathology in their early ages. Fourth,\u00a0there are patients who have triplication of APP that develop early onset AD with cerebral\u00a0amyloid angiopathy (CAA). This evidence suggests that A\u03b2\u00a0may be central to the disease process. Consequently, recent therapeutic strategies have\u00a0been designed to reduce production of A\u03b2, enhance clearance of A\u03b2, and prevent\u00a0formation of oligomeric species of A\u03b2\u00a0which damage neurons and synapses.<\/p>\n

A\u03b2\u00a0is cleaved from amyloid precursor protein (APP) by \u03b2\u00a0<\/a>and \u03b3-secretases<\/a> and is released\u00a0from mostly neurons into the brain interstitial fluid (ISF). This event happens in the\u00a0healthy brain throughout life. During AD progression, soluble A\u03b2\u00a0peptides start to\u00a0aggregate and accumulate in the toxic forms such as oligomers, fibrils, and plaques. It is\u00a0not identified yet whether the seed of amyloid plaques originates extracellularly or\u00a0intracellulary, but there is a evidence suggesting that initial step for amyoid plauqes formation and growth could occur in the extracellular space. Regardless of the origin of amyloid plaques, A\u03b2\u00a0peptides in the ISF seem to be\u00a0important in amyloid plaque formation, and the process of A\u03b2\u00a0aggregation is believed to\u00a0be concentration dependent in the brain extracellular space.\u00a0Therefore, understanding how A\u03b2\u00a0is regulated in the brain ISF is important in\u00a0understanding AD pathogenesis.<\/p>\n

Accumulating evidence suggests a direct relationship between neuronal\/synaptic\u00a0activity and A\u03b2\u00a0metabolism. APP is transported from entorhinal cortex to the\u00a0hippocampal formation via the perforant pathway, and lesioning this pathway results in\u00a0substantially less A\u03b2\u00a0deposition in the hippocampus in human APP transgenic mice. Decreasing neuronal\/synaptic activity over 24-48 hours reduces\u00a0steady-state A\u03b2\u00a0levels in media using hippocampal slice cultures in human APP\u00a0transgenic mice. Using an in vivo microdialysis technique\u00a0simultaneously with field potential recordings, Cirrito et al. showed that A\u03b2\u00a0levels in the\u00a0brain interstitial fluid are directly influenced by synaptic activity and synaptic vesicle\u00a0release over minutes to hours.<\/p>\n

 <\/p>\n

Reference:<\/p>\n

Jae-Eun Kang. AMYLOID-p REGULATION IN THE BRAIN INTERSTITIAL FLUID OF\u00a0A MOUSE MODEL OF ALZHEIMER’S DISEASE<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

The clinical\u00a0symptoms and signs of Alzheimer’s disease (AD)\u00a0result from abnormalities associated with neuronal\u00a0dysfunction and cell death in specific brain regions which are important in memory and\u00a0cognitive functions. Damaged circuits include […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[181],"tags":[225],"_links":{"self":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/596"}],"collection":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/comments?post=596"}],"version-history":[{"count":2,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/596\/revisions"}],"predecessor-version":[{"id":748,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/posts\/596\/revisions\/748"}],"wp:attachment":[{"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/media?parent=596"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/categories?post=596"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.bocsci.com\/blog\/wp-json\/wp\/v2\/tags?post=596"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}