Tags

Type your tag names separated by a space and hit enter

Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2.
J Neurosci 2008; 28(7):1537-45JN

Abstract

Alzheimer's disease (AD) is characterized by three primary pathologies in the brain: amyloid plaques, neurofibrillary tangles, and neuron loss. Mouse models have been useful for studying components of AD but are limited in their ability to fully recapitulate all pathologies. We crossed the APPSwDI transgenic mouse, which develops amyloid beta (Abeta)-protein deposits only, with a nitric oxide synthase 2 (NOS2) knock-out mouse, which develops no AD-like pathology. APPSwDI/NOS2(-/-) mice displayed impaired spatial memory compared with the APPSwDI mice, yet they have unaltered levels of Abeta. APPSwDI mice do not show tau pathology, whereas APPSwDI/NOS2(-/-) mice displayed extensive tau pathology associated with regions of dense microvascular amyloid deposition. Also, APPSwDI mice do not have any neuron loss, whereas the APPSwDI/NOS2(-/-) mice have significant neuron loss in the hippocampus and subiculum. Neuropeptide Y neurons have been shown to be particularly vulnerable in AD. These neurons appear to be particularly vulnerable in the APPSwDI/NOS2(-/-) mice as we observe a dramatic reduction in the number of NPY neurons in the hippocampus and subiculum. These data show that removal of NOS2 from an APP transgenic mouse results in development of a much greater spectrum of AD-like pathology and behavioral impairments.

Authors+Show Affiliations

Division of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA.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

Language

eng

PubMed ID

18272675

Citation

Wilcock, Donna M., et al. "Progression of Amyloid Pathology to Alzheimer's Disease Pathology in an Amyloid Precursor Protein Transgenic Mouse Model By Removal of Nitric Oxide Synthase 2." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 28, no. 7, 2008, pp. 1537-45.
Wilcock DM, Lewis MR, Van Nostrand WE, et al. Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2. J Neurosci. 2008;28(7):1537-45.
Wilcock, D. M., Lewis, M. R., Van Nostrand, W. E., Davis, J., Previti, M. L., Gharkholonarehe, N., ... Colton, C. A. (2008). Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 28(7), pp. 1537-45. doi:10.1523/JNEUROSCI.5066-07.2008.
Wilcock DM, et al. Progression of Amyloid Pathology to Alzheimer's Disease Pathology in an Amyloid Precursor Protein Transgenic Mouse Model By Removal of Nitric Oxide Synthase 2. J Neurosci. 2008 Feb 13;28(7):1537-45. PubMed PMID: 18272675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Progression of amyloid pathology to Alzheimer's disease pathology in an amyloid precursor protein transgenic mouse model by removal of nitric oxide synthase 2. AU - Wilcock,Donna M, AU - Lewis,Matthew R, AU - Van Nostrand,William E, AU - Davis,Judianne, AU - Previti,Mary Lou, AU - Gharkholonarehe,Nastaran, AU - Vitek,Michael P, AU - Colton,Carol A, PY - 2008/2/15/pubmed PY - 2008/2/26/medline PY - 2008/2/15/entrez SP - 1537 EP - 45 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 28 IS - 7 N2 - Alzheimer's disease (AD) is characterized by three primary pathologies in the brain: amyloid plaques, neurofibrillary tangles, and neuron loss. Mouse models have been useful for studying components of AD but are limited in their ability to fully recapitulate all pathologies. We crossed the APPSwDI transgenic mouse, which develops amyloid beta (Abeta)-protein deposits only, with a nitric oxide synthase 2 (NOS2) knock-out mouse, which develops no AD-like pathology. APPSwDI/NOS2(-/-) mice displayed impaired spatial memory compared with the APPSwDI mice, yet they have unaltered levels of Abeta. APPSwDI mice do not show tau pathology, whereas APPSwDI/NOS2(-/-) mice displayed extensive tau pathology associated with regions of dense microvascular amyloid deposition. Also, APPSwDI mice do not have any neuron loss, whereas the APPSwDI/NOS2(-/-) mice have significant neuron loss in the hippocampus and subiculum. Neuropeptide Y neurons have been shown to be particularly vulnerable in AD. These neurons appear to be particularly vulnerable in the APPSwDI/NOS2(-/-) mice as we observe a dramatic reduction in the number of NPY neurons in the hippocampus and subiculum. These data show that removal of NOS2 from an APP transgenic mouse results in development of a much greater spectrum of AD-like pathology and behavioral impairments. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/18272675/Progression_of_amyloid_pathology_to_Alzheimer's_disease_pathology_in_an_amyloid_precursor_protein_transgenic_mouse_model_by_removal_of_nitric_oxide_synthase_2_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=18272675 DB - PRIME DP - Unbound Medicine ER -