{"id":4595,"date":"2020-06-26T21:14:23","date_gmt":"2020-06-27T01:14:23","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/the-human-brain-ngf-metabolic-pathway-is-impaired-in-the-pre-clinical-and-clinical-continuum-of-alzheimers-disease-2\/"},"modified":"2024-12-03T14:57:07","modified_gmt":"2024-12-03T19:57:07","slug":"the-human-brain-ngf-metabolic-pathway-is-impaired-in-the-pre-clinical-and-clinical-continuum-of-alzheimers-disease-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/the-human-brain-ngf-metabolic-pathway-is-impaired-in-the-pre-clinical-and-clinical-continuum-of-alzheimers-disease-2\/","title":{"rendered":"The human brain NGF metabolic pathway is impaired in the pre-clinical and clinical continuum of Alzheimers disease"},"content":{"rendered":"<h2 id=\"Abs1\" class=\"c-article-section__title js-section-title js-c-reading-companion-sections-item\">Abstract<\/h2>\n<div id=\"Abs1-content\" class=\"c-article-section__content\">\n<p>The NGF metabolic pathway entails the proteins that mature pro-nerve growth factor (proNGF) to NGF and those that degrade NGF. Basal forebrain cholinergic neurons require NGF for maintenance of cholinergic phenotype, are critical for cognition, and degenerate early in Alzheimer\u2019s disease (AD). In AD, NGF metabolism is altered, but it is not known whether this is an early phenomenon, nor how it relates to AD pathology and symptomology. We acquired dorsolateral\/medial prefrontal cortex samples from individuals with Alzheimer\u2019s dementia, Mild Cognitive Impairment (MCI), or no cognitive impairment with high (HA-NCI) and low (LA-NCI) brain A\u03b2 from the Religious Orders Study. Cortical proNGF protein, but not mRNA, was higher in AD, MCI, and HA-NCI, while mature NGF was lower. Plasminogen protein was higher in MCI and AD brain tissue, with plasminogen mRNA not\u00a0likewise elevated, suggesting diminished activation of the proNGF convertase, plasmin. The plasminogen activator tPA was lower in HA-NCI while neuroserpin, the CNS tPA inhibitor, was higher in AD and MCI cortical samples. Matrix metalloproteinase 9 (MMP9), which degrades NGF, was overactive in MCI and AD. Transcription of the MMP9 inhibitor TIMP1 was lower in HA-NCI. ProNGF levels correlated with plasminogen, neuroserpin, and VAChT while NGF correlated with MMP9 activity. In NCI, proNGF correlated with cerebral A\u03b2 and tau deposition and to cognitive performance. In summary, proNGF maturation is impaired in preclinical and clinical AD while mature NGF degradation is enhanced. These differences correlate with cognition, pathology, and cholinergic tone, and may suggest novel biomarkers and therapeutic targets.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4595","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>The human brain NGF metabolic pathway is impaired in the pre-clinical and clinical continuum of Alzheimers disease - CCNA - CCNV<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/the-human-brain-ngf-metabolic-pathway-is-impaired-in-the-pre-clinical-and-clinical-continuum-of-alzheimers-disease-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The human brain NGF metabolic pathway is impaired in the pre-clinical and clinical continuum of Alzheimers disease - 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