{"id":4519,"date":"2020-06-19T15:19:21","date_gmt":"2020-06-19T19:19:21","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/regional-progression-of-alzheimers-disease-confounds-behavioural-rescue-after-amyloid-attenuation-2\/"},"modified":"2024-12-03T14:56:54","modified_gmt":"2024-12-03T19:56:54","slug":"regional-progression-of-alzheimers-disease-confounds-behavioural-rescue-after-amyloid-attenuation-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/regional-progression-of-alzheimers-disease-confounds-behavioural-rescue-after-amyloid-attenuation-2\/","title":{"rendered":"Regional progression of Alzheimer\u2019s disease confounds behavioural rescue after amyloid attenuation"},"content":{"rendered":"

Abstract<\/h2>\n
\n

Failure of Alzheimer\u2019s disease clinical trials to improve or stabilize cognition has led to the need for a better understanding of the driving forces behind cognitive decline in the presence of active disease processes. To dissect contributions of individual pathologies to cognitive function, we used the TgF344-AD rat model, which recapitulates the salient hallmarks of Alzheimer\u2019s disease pathology observed in patient populations (amyloid, tau inclusions, frank neuronal loss, and cognitive deficits).\u00a0scyllo<\/em>-Inositol treatment attenuated amyloid-\u03b2 peptide in disease-bearing TgF344-AD rats, which rescued pattern separation in the novel object recognition task and executive function in the reversal learning phase of the Barnes maze. Interestingly, neither activities of daily living in the burrowing task nor spatial memory in the Barnes maze were rescued by attenuating amyloid-\u03b2 peptide. To understand the pathological correlates leading to behavioural rescue, we examined the neuropathology and\u00a0in vivo<\/em>\u00a0electrophysiological signature of the hippocampus. Amyloid-\u03b2 peptide attenuation reduced hippocampal tau pathology and rescued adult hippocampal neurogenesis and neuronal function, via improvements in cross-frequency coupling between theta and gamma bands. To investigate mechanisms underlying the persistence of spatial memory deficits, we next examined neuropathology in the entorhinal cortex, a region whose input to the hippocampus is required for spatial memory. Reduction of amyloid-\u03b2 peptide in the entorhinal cortex had no effect on entorhinal tau pathology or entorhinal-hippocampal neuronal network dysfunction, as measured by an impairment in hippocampal response to entorhinal stimulation. Thus, rescue or not of cognitive function is dependent on regional differences of amyloid-\u03b2, tau and neuronal network dysfunction, demonstrating the importance of staging disease in patients prior to enrolment in clinical trials. These results further emphasize the need for combination therapeutic approaches across disease progression.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4519","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"\nRegional progression of Alzheimer\u2019s disease confounds behavioural rescue after amyloid attenuation - 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\/regional-progression-of-alzheimers-disease-confounds-behavioural-rescue-after-amyloid-attenuation-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Regional progression of Alzheimer\u2019s disease confounds behavioural rescue after amyloid attenuation - 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