{"id":9651,"date":"2024-09-13T22:49:45","date_gmt":"2024-09-13T14:49:45","guid":{"rendered":"http:\/\/zestmag.com\/online\/?p=9651"},"modified":"2024-09-13T22:50:04","modified_gmt":"2024-09-13T14:50:04","slug":"boosting-brain-protein-levels-may-slow-decline-from-alzheimers","status":"publish","type":"post","link":"http:\/\/zestmag.com\/online\/boosting-brain-protein-levels-may-slow-decline-from-alzheimers\/","title":{"rendered":"Boosting brain protein levels may slow decline from Alzheimer\u2019s"},"content":{"rendered":"\n

A study published in the journal Brain<\/a><\/em> shows that increases in protein levels with new Alzheimer\u2019s drugs can explain the slowing of cognitive impairment at least as well as the reduction in amyloid plaques.\u00a0<\/strong><\/p>\n\n\n\n

During a study challenging the idea that newly approved monoclonal antibodies reduce cognitive decline in Alzheimer’s patients by clearing amyloid, University of Cincinnati researchers found that the unintended increase in levels of a critical brain protein correlates equally well with cognitive benefits. <\/p>\n\n\n\n

Led by UC\u2019s Alberto Espay, MD, the research was published in the journal Brain<\/em> on Sept. 11. <\/p>\n\n\n\n

Study background <\/h3>\n\n\n\n

For decades, the prevailing theory in the field has stated that a protein made up of 42 amino acids called amyloid-beta 42 (A\u03b242) hardens into clumps called amyloid plaques, and those plaques damage the brain, causing Alzheimer\u2019s disease. <\/p>\n\n\n\n

Espay and team have hypothesized<\/a> that normal, soluble A\u03b242 in the brain is crucial for neuron health and that the loss of A\u03b242, rather than the buildup of plaques, drives Alzheimer\u2019s. This includes published research<\/a> that suggests dementia occurs not when plaque levels are high but when A\u03b242 levels drop very low. <\/p>\n\n\n\n

According to Espay\u2019s research, the transformation of A\u03b242 into plaques appears to be the brain\u2019s normal response to biological, metabolic or infectious stress. <\/p>\n\n\n\n

\u201cMost of us will accrue amyloid plaques in our brains as we age, and yet very few of us with plaques go on to develop dementia,\u201d said Espay, professor of neurology in the UC College of Medicine and director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson\u2019s Disease and Movement Disorders at the UC Gardner Neuroscience Institute. \u201cYet the plaques remain the center of our attention in biomarker development and therapeutic strategies.\u201d <\/p>\n\n\n\n

Study details <\/h3>\n\n\n\n

Recently, several new monoclonal antibody medications designed to remove amyloid from the brain were approved after showing they lessened cognitive decline in clinical trials. <\/p>\n\n\n\n

Espay and his colleagues noticed that these drugs unintentionally increased levels of A\u03b242.  <\/p>\n\n\n\n

\u201cAmyloid plaques don\u2019t cause Alzheimer\u2019s, but if the brain makes too much of it while defending against infections, toxins or biological changes, it can\u2019t produce enough A\u03b242, causing its levels to drop below a critical threshold,\u201d Espay explained. \u201cThat\u2019s when dementia symptoms emerge.\u201d <\/p>\n\n\n\n

The team analyzed data from nearly 26,000 patients enrolled in 24 randomized clinical trials of these new antibody treatments, assessing cognitive impairment and differences in levels of A\u03b242 before and after treatment. They found that higher levels of A\u03b242 after treatment were independently associated with slower cognitive impairment and clinical decline.  <\/p>\n\n\n\n

\u201cAll stories have two sides \u2014 even the one we have told ourselves about how anti-amyloid treatments work: by lowering amyloid,\u201d Espay said. \u201cIn fact, they also raise the levels of A\u03b242. Even if this is unintended, it is why there may be a benefit. Our study shows that we can predict changes in cognitive outcomes in anti-amyloid trials at least as well by the increases in A\u03b242 as by the decreases in amyloid.\u201d <\/p>\n\n\n\n

Espay said these findings fit well into his larger hypothesis about the root cause of Alzheimer\u2019s, as increasing levels of A\u03b242 appear to improve cognition.  <\/p>\n\n\n\n

\u201cIf the problem with Alzheimer\u2019s is the loss of the normal protein, then increasing it should be beneficial, and this study showed that it is,\u201d he said. \u201cThe story makes sense: Increasing A\u03b242 levels to within the normal range is desirable.\u201d <\/p>\n\n\n\n

However, Espay believes these results also present a conundrum for clinicians because removing amyloid from the brain is toxic and may cause the brain to shrink faster after antibody treatment. <\/p>\n\n\n\n

\u201cDo we give patients an anti-protein treatment to increase their protein levels? I think the end, increasing A\u03b242, doesn\u2019t justify the means, decreasing amyloid,\u201d Espay said. Therapies that directly increase A\u03b242 levels without targeting amyloid are a focus of research for Espay and his group. <\/p>\n\n\n\n

Other coauthors of the study include UC\u2019s Jesus Abanto, Alok K. Dwivedi of Texas Tech University and Bruno P. Imbimbo of Chiesi Farmaceutici of Parma, Italy<\/p>\n","protected":false},"excerpt":{"rendered":"

A study published in the journal Brain shows that increases in protein levels with new Alzheimer\u2019s drugs can explain the slowing of cognitive impairment at least as well as the reduction in amyloid plaques.\u00a0 During a study challenging the idea that newly approved monoclonal antibodies reduce cognitive decline in Alzheimer’s patients by clearing amyloid, University […]<\/p>\n","protected":false},"author":3,"featured_media":9660,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[921,1140,2348],"class_list":["post-9651","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-newsmakers","tag-alzheimers-disease","tag-senior-care","tag-senior-health"],"_links":{"self":[{"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/posts\/9651","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/comments?post=9651"}],"version-history":[{"count":1,"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/posts\/9651\/revisions"}],"predecessor-version":[{"id":9661,"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/posts\/9651\/revisions\/9661"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/media\/9660"}],"wp:attachment":[{"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/media?parent=9651"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/categories?post=9651"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/zestmag.com\/online\/wp-json\/wp\/v2\/tags?post=9651"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}