{"id":208,"date":"2022-11-05T15:11:47","date_gmt":"2022-11-05T15:11:47","guid":{"rendered":"http:\/\/johnhealth.blog\/?p=208"},"modified":"2022-11-05T15:11:47","modified_gmt":"2022-11-05T15:11:47","slug":"researchers-show-nmn-improves-cognitive-deficits-in-alzheimers","status":"publish","type":"post","link":"http:\/\/johnhealth.blog\/?p=208","title":{"rendered":"Researchers Show NMN Improves Cognitive Deficits in Alzheimer\u2019s"},"content":{"rendered":"<p class=\"subtitle\">Chinese scientists find that boosting NAD+ with its precursor, NMN improves the learning and memory of a mouse model for Alzheimer\u2019s disease.<\/p>\n<div class=\"single-article-image\">\n<div class=\"main-image\"><\/div>\n<p><small class=\"main-image-src\">Microglia cells stained for CD38, an NAD+ degrading enzyme | Hu et al., 2022<\/small><\/div>\n<div class=\"content-header\">\n<div class=\"author-and-date\">\n<div class=\"author\">By\u00a0<span class=\"main-color-g\">Victor Ciardha<\/span><\/div>\n<div class=\"date\"><time>Published:\u00a03:30 p.m. PST Jul 18, 2022\u00a0| Updated:\u00a010:07 am PST Aug 26, 2022<\/time><\/div>\n<\/div>\n<div>\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n<div class=\"content-def main-content\">\n<p><strong><em>Highlights:\u00a0<\/em><\/strong><\/p>\n<ul>\n<li><em>Treating Alzheimer\u2019s disease (AD) mice with NMN improves their learning and memory.\u00a0<\/em><\/li>\n<li><em>NMN restores energy metabolism, reduces inflammation, and eliminates beta-amyloid, a hallmark of AD.<\/em><\/li>\n<li><em>Inhibiting an enzyme that degrades NAD+ called CD38 also reverses AD dysfunction.\u00a0<\/em><\/li>\n<\/ul>\n<p>While the accumulation of a protein called beta-amyloid (A\u03b2) is undoubtedly involved, the underlying cause of AD is still a mystery. And as the search for a cure continues, a new study published in\u00a0<a href=\"https:\/\/link.springer.com\/article\/10.1186\/s40659-022-00379-1\" target=\"_blank\" rel=\"noopener\"><em>Biological Research<\/em><\/a>\u00a0has shown that NAD+, an essential molecule needed to produce the energy of all cells, may play a key role.<\/p>\n<p>In the study, Hu and colleagues from the Shanghai Geriatric Institute of Chinese Medicine reveal that boosting NAD+ reverses AD defects in a mouse model for AD. The researchers treated AD mice with either NMN, an NAD+ precursor that promotes the synthesis of NAD+, or a CD38 inhibitor (antibody). As an NAD+ degrading enzyme that increases with age, CD38 is considered the primary contributor to age-related NAD+ decline. The results showed that NMN or the CD38 inhibitor improve the learning and memory of AD mice and reduces inflammation, a hallmark of aging. Furthermore, boosting NAD+ decreases the prevalence of A\u03b2.<\/p>\n<h2>Boosting NAD+ Reverses Alzheimer\u2019s Disease Defects<\/h2>\n<p>Demonstrating the cognitive deficits associated with AD, Hu and colleagues showed that AD mice perform worse on learning and memory tests than aged mice without AD. However, the learning and memory of AD mice improved after treatment with NMN or the CD38 inhibitor, suggesting that boosting NAD+ could improve the cognitive deficits associated with AD.<\/p>\n<figure class=\"wp-block-image size-large is-resized\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-8763\" src=\"https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Memory.png\" sizes=\"auto, (max-width: 612px) 100vw, 612px\" srcset=\"https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Memory.png 816w, https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Memory-300x90.png 300w, https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Memory-768x231.png 768w\" alt=\"\" width=\"612\" height=\"184\" \/><figcaption>(<a href=\"https:\/\/link.springer.com\/article\/10.1186\/s40659-022-00379-1#Ack1\" target=\"_blank\" rel=\"noopener\">Hu et al., 2022 |\u00a0<em>Biological Research<\/em><\/a>)\u00a0<strong>Learning and Memory are Improved by NMN and CD38 Inhibition.<\/strong>\u00a0Relative to typically aged mice (black \u2013 control group), untreated AD mice (red \u2013 model group) have reduced learning and memory scores,\u00a0 measured by new object recognition (left) and platform crossings (right). However, AD mice treated with a CD38 inhibitor (pink \u2013 CD38 inhibitor group) or NMN (blue \u2013 NMN group) show improvements in both measurements compared to untreated AD mice.<\/figcaption><\/figure>\n<p>Microglia cells are responsible for degrading harmful brain material such as excess A\u03b2. However, this degrading process (phagocytosis and autophagy) is slow and promotes inflammation. Thus, if microglia cannot keep up with the production of A\u03b2, inflammation ensues without complete A\u03b2 removal. To exacerbate it all, A\u03b2 can inhibit this critical function of microglia, allowing inflammation to persist, and causing progressive damage to neurons, leading to neuron cell death (neurodegeneration) and cognitive decline.<\/p>\n<p>Maintaining the energy metabolism of microglia is essential for sustaining their A\u03b2-degrading function. NAD+ supports energy metabolism by facilitating the production of ATP, a molecule that cells use for energy. In aged microglia cells, low NAD+ and ATP make these immune cells less efficient or incapable of degrading A\u03b2. Thus, boosting NAD+ could increase the production of ATP, reviving the destructive power of microglia.<\/p>\n<p>Hu and colleagues showed that NMN or CD38 inhibition increased the concentration of NAD+ and ATP in the brains of AD mice while reducing inflammation. These findings suggest that boosting NAD+ restores energy metabolism and reduces inflammation in AD mice, which could explain the observed improvements in learning and memory.<\/p>\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" class=\"wp-image-8824\" src=\"https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Picture1-2-1.png\" sizes=\"(max-width: 908px) 100vw, 908px\" srcset=\"https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Picture1-2-1.png 908w, https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Picture1-2-1-300x94.png 300w, https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Picture1-2-1-768x239.png 768w\" alt=\"\" \/><figcaption>(<a href=\"https:\/\/link.springer.com\/article\/10.1186\/s40659-022-00379-1#Ack1\" target=\"_blank\" rel=\"noopener\">Hu et al., 2022 |\u00a0<em>Biological Research<\/em><\/a>)\u00a0<strong>Energy Metabolism is Reinvigorated by NMN and CD38 Inhibition.\u00a0<\/strong>In the hippocampus, the brain region associated with learning and memory, AD mice have lower NAD+ and ATP.\u00a0 Treatment with either CD38 inhibition or NMN increases NAD+ and ATP levels.<\/figcaption><\/figure>\n<p>Microglia cells take different forms; in their active form, they become harmful and produce inflammatory molecules. Hu and colleagues showed that boosting NAD+ reduces microglial activation and eliminates A\u03b2 from AD mouse brains. These findings suggest that increasing NAD+ levels restores the destructive capacity of microglia cells, enabling them to rid the brain of harmful A\u03b2 deposits.<\/p>\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" class=\"wp-image-8826\" src=\"https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Picture2-2.png\" sizes=\"(max-width: 902px) 100vw, 902px\" srcset=\"https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Picture2-2.png 902w, https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Picture2-2-300x79.png 300w, https:\/\/cms.nmn.com\/wp-content\/uploads\/2022\/07\/Picture2-2-768x203.png 768w\" alt=\"\" \/><figcaption>(<a href=\"https:\/\/link.springer.com\/article\/10.1186\/s40659-022-00379-1#Ack1\" target=\"_blank\" rel=\"noopener\">Hu et al., 2022 |\u00a0<em>Biological Research<\/em><\/a>)\u00a0<strong>NMN and CD38 Inhibition Rid the Brain of A\u03b2.\u00a0<\/strong>Amyloid plaques, measured with green fluorescent staining (green), were increased in untreated AD mice (model group), but reduced by a CD38 inhibitor (CD38 inhibitor group) or NMN (NMN group).<\/p>\n<\/figcaption><\/figure>\n<h2>Can Boosting NAD+ Treat Alzheimer\u2019s?<\/h2>\n<p>Overall, the findings of Hu and colleagues suggest that boosting NAD+ by inhibiting CD38 or supplementing with NMN revives aged microglia cells, allowing them to destroy A\u03b2 and reduce inflammation in AD mice. This reduction in inflammation could lead to improvements in learning and memory.\u00a0<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6929692\/\" target=\"_blank\" rel=\"noopener\">Another study<\/a>\u00a0showed that genetically removing CD38 can improve the memory of AD mice. Furthermore, boosting NAD+ with another precursor, NR, has\u00a0<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1111\/jnc.15367\" target=\"_blank\" rel=\"noopener\">been shown<\/a>\u00a0to reduce neuroinflammation, possibly leading to improved cognitive performance. Indeed, a recent study showed that reducing inflammation with a molecule called\u00a0<a href=\"https:\/\/journals.sagepub.com\/doi\/full\/10.1177\/1934578X221111029\" target=\"_blank\" rel=\"noopener\">saikogenin F<\/a>\u00a0improves the learning and memory of AD mice.<\/p>\n<p>While these animal studies make boosting NAD+ seem like a promising treatment for AD, there are not enough human studies to validate the findings. For example,\u00a0<a href=\"https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1111\/acel.13658\" target=\"_blank\" rel=\"noopener\">a recent study<\/a>\u00a0showed that while NR and caffeine raise NAD+ and ATP levels in cells cultured from AD patients, it does not improve metabolic parameters. However, it is unclear from this study whether NR and caffeine could improve cognitive performance in AD patients. Thus, the effect of boosting NAD+ on cognitive performance in AD patients still needs to be tested, but the prospects seem promising.<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<div class=\"collapse-container\">\n<div class=\"trigger-container\">\n<div class=\"toggle\">Model and Dosage<\/div>\n<\/div>\n<div class=\"content-container \">\n<div class=\"source-content\">\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"footer-content\">\n<div class=\"footer-block\">\n<div class=\"header\">Story Source<\/div>\n<div class=\"content\">\n<p>Hu Y, Huang Y, Xing S, Chen C, Shen D, Chen J. A\u03b2 promotes CD38 expression in senescent microglia in Alzheimer\u2019s disease. Biol Res. 2022 Mar 3;55(1):10. doi: 10.1186\/s40659-022-00379-1. PMID: 35241173; PMCID: PMC8892694.<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n<div class=\"footer-block\">\n<div class=\"header\">Journal Reference<\/div>\n<div class=\"content\">\n<p>Blacher E, Dadali T, Bespalko A, Haupenthal VJ, Grimm MO, Hartmann T, Lund FE, Stein R, Levy A. Alzheimer\u2019s disease pathology is attenuated in a CD38-deficient mouse model. Ann Neurol. 2015 Jul;78(1):88-103. doi: 10.1002\/ana.24425. Epub 2015 May 25. PMID: 25893674; PMCID: PMC6929692.<\/p>\n<p>&nbsp;<\/p>\n<p>Roboon J, Hattori T, Ishii H, Takarada-Iemata M, Nguyen DT, Heer CD, O\u2019Meally D, Brenner C, Yamamoto Y, Okamoto H, Higashida H, Hori O. Inhibition of CD38 and supplementation of nicotinamide riboside ameliorate lipopolysaccharide-induced microglial and astrocytic neuroinflammation by increasing NAD. J Neurochem. 2021 Jul;158(2):311-327. doi: 10.1111\/jnc.15367. Epub 2021 May 9. PMID: 33871064; PMCID: PMC8282715.<\/p>\n<p>&nbsp;<\/p>\n<p>Chen Z-H, Li J, Zhao X-X, et al. Saikogenin F From Bupleurum smithii Ameliorates Learning and Memory Impairment via Antiinflammation Effect in an Alzheimer\u2019s Disease Mouse Model. Natural Product Communications. July 2022. doi:10.1177\/1934578X221111029<\/p>\n<p>&nbsp;<\/p>\n<p>Ryu WI, Shen M, Lee Y, Healy RA, Bormann MK, Cohen BM, Sonntag KC. Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer\u2019s disease. Aging Cell. 2022 Jun 21:e13658. doi: 10.1111\/acel.13658. Epub ahead of print. PMID: 35730144.<\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Chinese scientists find that boosting NAD+ with its precursor, NMN improves the learning and memory of a mouse model for Alzheimer\u2019s disease. Microglia cells stained for CD38, an NAD+ degrading enzyme | Hu et al., 2022 By\u00a0Victor Ciardha Published:\u00a03:30 p.m. PST Jul 18, 2022\u00a0| Updated:\u00a010:07 am PST Aug 26, 2022 &nbsp; Highlights:\u00a0 Treating Alzheimer\u2019s disease (AD) mice with NMN improves [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":209,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[47,46,6,48],"class_list":["post-208","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-nmn","tag-alzheimer","tag-cognitive-deficits","tag-nmn","tag-research"],"_links":{"self":[{"href":"http:\/\/johnhealth.blog\/index.php?rest_route=\/wp\/v2\/posts\/208","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/johnhealth.blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/johnhealth.blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/johnhealth.blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/johnhealth.blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=208"}],"version-history":[{"count":1,"href":"http:\/\/johnhealth.blog\/index.php?rest_route=\/wp\/v2\/posts\/208\/revisions"}],"predecessor-version":[{"id":210,"href":"http:\/\/johnhealth.blog\/index.php?rest_route=\/wp\/v2\/posts\/208\/revisions\/210"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/johnhealth.blog\/index.php?rest_route=\/wp\/v2\/media\/209"}],"wp:attachment":[{"href":"http:\/\/johnhealth.blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=208"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/johnhealth.blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=208"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/johnhealth.blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=208"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}