Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice
Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L.
Rockefeller University Press
Published 2018
Rockefeller University Press
Published 2018
| Publication Date: |
2018-05-08
|
|---|---|
| Publisher: |
Rockefeller University Press
|
| Print ISSN: |
0022-1007
|
| Electronic ISSN: |
1540-9538
|
| Topics: |
Medicine
|
| Keywords: |
Neuroscience
|
| Published by: |
| _version_ | 1836398921618817024 |
|---|---|
| autor | Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. |
| beschreibung | Drug development for Alzheimer’s disease has endeavored to lower amyloid β (Aβ) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aβ has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aβ production with passive anti-Aβ immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aβ production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aβ as the primary driver of cognitive recovery. |
| citation_standardnr | 6253102 |
| datenlieferant | ipn_articles |
| feed_id | 96 |
| feed_publisher | Rockefeller University Press |
| feed_publisher_url | http://www.rupress.org/ |
| insertion_date | 2018-05-08 |
| journaleissn | 1540-9538 |
| journalissn | 0022-1007 |
| publikationsjahr_anzeige | 2018 |
| publikationsjahr_facette | 2018 |
| publikationsjahr_intervall | 7984:2015-2019 |
| publikationsjahr_sort | 2018 |
| publisher | Rockefeller University Press |
| quelle | Journal of Experimental Medicine |
| relation | http://jem.rupress.org/cgi/content/short/215/5/1349?rss=1 |
| schlagwort | Neuroscience |
| search_space | articles |
| shingle_author_1 | Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. |
| shingle_author_2 | Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. |
| shingle_author_3 | Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. |
| shingle_author_4 | Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. |
| shingle_catch_all_1 | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice Neuroscience Drug development for Alzheimer’s disease has endeavored to lower amyloid β (Aβ) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aβ has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aβ production with passive anti-Aβ immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aβ production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aβ as the primary driver of cognitive recovery. Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_2 | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice Neuroscience Drug development for Alzheimer’s disease has endeavored to lower amyloid β (Aβ) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aβ has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aβ production with passive anti-Aβ immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aβ production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aβ as the primary driver of cognitive recovery. Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_3 | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice Neuroscience Drug development for Alzheimer’s disease has endeavored to lower amyloid β (Aβ) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aβ has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aβ production with passive anti-Aβ immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aβ production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aβ as the primary driver of cognitive recovery. Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_catch_all_4 | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice Neuroscience Drug development for Alzheimer’s disease has endeavored to lower amyloid β (Aβ) by either blocking production or promoting clearance. The benefit of combining these approaches has been examined in mouse models and shown to improve pathological measures of disease over single treatment; however, the impact on cellular and cognitive functions affected by Aβ has not been tested. We used a controllable APP transgenic mouse model to test whether combining genetic suppression of Aβ production with passive anti-Aβ immunization improved functional outcomes over either treatment alone. Compared with behavior before treatment, arresting further Aβ production (but not passive immunization) was sufficient to stop further decline in spatial learning, working memory, and associative memory, whereas combination treatment reversed each of these impairments. Cognitive improvement coincided with resolution of neuritic dystrophy, restoration of synaptic density surrounding deposits, and reduction of hyperactive mammalian target of rapamycin signaling. Computational modeling corroborated by in vivo microdialysis pointed to the reduction of soluble/exchangeable Aβ as the primary driver of cognitive recovery. Chiang, A. C. A., Fowler, S. W., Savjani, R. R., Hilsenbeck, S. G., Wallace, C. E., Cirrito, J. R., Das, P., Jankowsky, J. L. Rockefeller University Press 0022-1007 00221007 1540-9538 15409538 |
| shingle_title_1 | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice |
| shingle_title_2 | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice |
| shingle_title_3 | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice |
| shingle_title_4 | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice |
| timestamp | 2025-06-30T23:34:46.134Z |
| titel | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice |
| titel_suche | Combination anti-A{beta} treatment maximizes cognitive recovery and rebalances mTOR signaling in APP mice |
| topic | WW-YZ |
| uid | ipn_articles_6253102 |