Asset Details
Do you wish to reserve the book?
Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline
Do you wish to request the book?
Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline
2012
Overview
Proinflammatory cytokine expression increases as a result of amyloid deposition in Alzheimer's disease. Frank L. Heppner and colleagues show that genetic and pharmacological inhibition of IL-12 and IL-23 signaling reduces plaque load and improves cognitive deficits in mouse models of Alzheimer's disease. As the concentration of p40 is also increased in the cerebrospinal fluid of individuals with Alzheimer's disease, this suggests that this pathway may be targeted therapeutically in patients.
The pathology of Alzheimer's disease has an inflammatory component that is characterized by upregulation of proinflammatory cytokines, particularly in response to amyloid-β (Aβ). Using the
APPPS1
Alzheimer's disease mouse model, we found increased production of the common interleukin-12 (IL-12) and IL-23 subunit p40 by microglia. Genetic ablation of the IL-12/IL-23 signaling molecules p40, p35 or p19, in which deficiency of p40 or its receptor complex had the strongest effect, resulted in decreased cerebral amyloid load. Although deletion of IL-12/IL-23 signaling from the radiation-resistant glial compartment of the brain was most efficient in mitigating cerebral amyloidosis, peripheral administration of a neutralizing p40-specific antibody likewise resulted in a reduction of cerebral amyloid load in
APPPS1
mice. Furthermore, intracerebroventricular delivery of antibodies to p40 significantly reduced the concentration of soluble Aβ species and reversed cognitive deficits in aged
APPPS1
mice. The concentration of p40 was also increased in the cerebrospinal fluid of subjects with Alzheimer's disease, which suggests that inhibition of the IL-12/IL-23 pathway may attenuate Alzheimer's disease pathology and cognitive deficits.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Alzheimer Disease - pathology
/ Amyloid beta-Peptides - metabolism
/ Animals
/ Antibodies - administration & dosage
/ Complications and side effects
/ Disease
/ Enzyme-Linked Immunosorbent Assay
/ Interleukin-12 Subunit p40 - cerebrospinal fluid
/ Interleukin-12 Subunit p40 - genetics
/ Interleukin-12 Subunit p40 - immunology
/ Interleukin-12 Subunit p40 - metabolism
/ Mice
/ Real-Time Polymerase Chain Reaction
