Tags

Type your tag names separated by a space and hit enter

Diverse inflammatory responses in transgenic mouse models of Alzheimer's disease and the effect of immunotherapy on these responses.
ASN Neuro. 2011 Nov 30; 3(5):249-58.AN

Abstract

While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT-PCR (reverse transcription-PCR) and protein analysis to measure inflammatory responses ranging from pro-inflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only (APPSw) and amyloid deposits with progression to tau pathology and neuron loss [APPSw/NOS2-/- (nitric oxide synthase 2-/-)]. We also examined tissues from previously published immunotherapy studies. These studies were a passive immunization study in APPSw mice and an active vaccination study in APPSw/NOS2-/- mice. Both studies have already been shown to lower amyloid load and improve cognition. We have found that amyloid deposition is associated with high expression of alternative activation and acquired deactivation genes and low expression of pro-inflammatory genes, whereas disease progression is associated with a mixed phenotype including increased levels of some classical activation factors. Immunotherapy targeting amyloid deposition in both mouse models resulted in decreased alternative inflammatory markers and, in the case of passive immunization, a transient increase in pro-inflammatory markers. Our results suggest that an alternative immune response favours retention of amyloid deposits in the brain, and switching away from this state by immunotherapy permits removal of amyloid.

Authors+Show Affiliations

Division of Neurology, Duke University Medical Center, Durham, NC 27710, U.S.A.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21995345

Citation

Wilcock, Donna M., et al. "Diverse Inflammatory Responses in Transgenic Mouse Models of Alzheimer's Disease and the Effect of Immunotherapy On These Responses." ASN Neuro, vol. 3, no. 5, 2011, pp. 249-58.
Wilcock DM, Zhao Q, Morgan D, et al. Diverse inflammatory responses in transgenic mouse models of Alzheimer's disease and the effect of immunotherapy on these responses. ASN Neuro. 2011;3(5):249-58.
Wilcock, D. M., Zhao, Q., Morgan, D., Gordon, M. N., Everhart, A., Wilson, J. G., Lee, J. E., & Colton, C. A. (2011). Diverse inflammatory responses in transgenic mouse models of Alzheimer's disease and the effect of immunotherapy on these responses. ASN Neuro, 3(5), 249-58. https://doi.org/10.1042/AN20110018
Wilcock DM, et al. Diverse Inflammatory Responses in Transgenic Mouse Models of Alzheimer's Disease and the Effect of Immunotherapy On These Responses. ASN Neuro. 2011 Nov 30;3(5):249-58. PubMed PMID: 21995345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diverse inflammatory responses in transgenic mouse models of Alzheimer's disease and the effect of immunotherapy on these responses. AU - Wilcock,Donna M, AU - Zhao,Qun, AU - Morgan,Dave, AU - Gordon,Marcia N, AU - Everhart,Angela, AU - Wilson,Joan G, AU - Lee,Jennifer E, AU - Colton,Carol A, Y1 - 2011/11/30/ PY - 2011/10/15/entrez PY - 2011/10/15/pubmed PY - 2012/4/24/medline SP - 249 EP - 58 JF - ASN neuro JO - ASN Neuro VL - 3 IS - 5 N2 - While the presence of an inflammatory response in AD (Alzheimer's disease) is well known, the data on inflammation are conflicting, suggesting that inflammation either attenuates pathology, exacerbates it or has no effect. Our goal was to more fully characterize the inflammatory response in APP (amyloid precursor protein) transgenic mice with and without disease progression. In addition, we have examined how anti-Aβ (amyloid β-peptide) immunotherapy alters this inflammatory response. We have used quantitative RT-PCR (reverse transcription-PCR) and protein analysis to measure inflammatory responses ranging from pro-inflammatory to anti-inflammatory and repair factors in transgenic mice that develop amyloid deposits only (APPSw) and amyloid deposits with progression to tau pathology and neuron loss [APPSw/NOS2-/- (nitric oxide synthase 2-/-)]. We also examined tissues from previously published immunotherapy studies. These studies were a passive immunization study in APPSw mice and an active vaccination study in APPSw/NOS2-/- mice. Both studies have already been shown to lower amyloid load and improve cognition. We have found that amyloid deposition is associated with high expression of alternative activation and acquired deactivation genes and low expression of pro-inflammatory genes, whereas disease progression is associated with a mixed phenotype including increased levels of some classical activation factors. Immunotherapy targeting amyloid deposition in both mouse models resulted in decreased alternative inflammatory markers and, in the case of passive immunization, a transient increase in pro-inflammatory markers. Our results suggest that an alternative immune response favours retention of amyloid deposits in the brain, and switching away from this state by immunotherapy permits removal of amyloid. SN - 1759-0914 UR - https://www.unboundmedicine.com/medline/citation/21995345/Diverse_inflammatory_responses_in_transgenic_mouse_models_of_Alzheimer's_disease_and_the_effect_of_immunotherapy_on_these_responses_ L2 - http://journals.sagepub.com/doi/full/10.1042/AN20110018?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -