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Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer's disease transgenic mouse model.
J Neurochem. 2011 Sep; 118(5):928-38.JN

Abstract

Amyloid-beta (Aβ) plaques are a hallmark of Alzheimer's disease. Several proteases including plasmin are thought to promote proteolytic cleavage and clearance of Aβ from brain. The activity of both plasmin and tissue plasminogen activator are reduced in Alzheimer's disease brain, while the tissue plasminogen activator inhibitor neuroserpin is up-regulated. Here, the relationship of tissue plasminogen activator and neuroserpin to Aβ levels is explored in mouse models. Aβ(1-42) peptide injected into the frontal cortex of tissue plasminogen activator knockout mice is slow to disappear compared to wildtype mice, whereas neuroserpin knockout mice show a rapid clearance of Aβ(1-42). The relationship of neuroserpin and tissue plasminogen activator to Aβ plaque formation was studied further by knocking-out neuroserpin in the human amyloid precursor protein-J20 transgenic mouse. Compared to the J20-transgenic mouse, the neuroserpin-deficient J20-transgenic mice have a dramatic reduction of Aβ peptides, fewer and smaller plaques, and more active tissue plasminogen activator associated with plaques. Furthermore, neuroserpin-deficient J20-transgenic mice have near normal performances in the Morris water maze, in contrast to the spatial memory defects seen in J20-transgenic mice. These results support the concept that neuroserpin inhibition of tissue plasminogen activator plays an important role both in the accumulation of brain amyloid plaques and loss of cognitive abilities.

Authors+Show Affiliations

Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21689108

Citation

Fabbro, Shay, et al. "Amyloid-beta Levels Are Significantly Reduced and Spatial Memory Defects Are Rescued in a Novel Neuroserpin-deficient Alzheimer's Disease Transgenic Mouse Model." Journal of Neurochemistry, vol. 118, no. 5, 2011, pp. 928-38.
Fabbro S, Schaller K, Seeds NW. Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer's disease transgenic mouse model. J Neurochem. 2011;118(5):928-38.
Fabbro, S., Schaller, K., & Seeds, N. W. (2011). Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer's disease transgenic mouse model. Journal of Neurochemistry, 118(5), 928-38. https://doi.org/10.1111/j.1471-4159.2011.07359.x
Fabbro S, Schaller K, Seeds NW. Amyloid-beta Levels Are Significantly Reduced and Spatial Memory Defects Are Rescued in a Novel Neuroserpin-deficient Alzheimer's Disease Transgenic Mouse Model. J Neurochem. 2011;118(5):928-38. PubMed PMID: 21689108.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer's disease transgenic mouse model. AU - Fabbro,Shay, AU - Schaller,Kristin, AU - Seeds,Nicholas W, Y1 - 2011/07/18/ PY - 2011/6/22/entrez PY - 2011/6/22/pubmed PY - 2011/10/15/medline SP - 928 EP - 38 JF - Journal of neurochemistry JO - J. Neurochem. VL - 118 IS - 5 N2 - Amyloid-beta (Aβ) plaques are a hallmark of Alzheimer's disease. Several proteases including plasmin are thought to promote proteolytic cleavage and clearance of Aβ from brain. The activity of both plasmin and tissue plasminogen activator are reduced in Alzheimer's disease brain, while the tissue plasminogen activator inhibitor neuroserpin is up-regulated. Here, the relationship of tissue plasminogen activator and neuroserpin to Aβ levels is explored in mouse models. Aβ(1-42) peptide injected into the frontal cortex of tissue plasminogen activator knockout mice is slow to disappear compared to wildtype mice, whereas neuroserpin knockout mice show a rapid clearance of Aβ(1-42). The relationship of neuroserpin and tissue plasminogen activator to Aβ plaque formation was studied further by knocking-out neuroserpin in the human amyloid precursor protein-J20 transgenic mouse. Compared to the J20-transgenic mouse, the neuroserpin-deficient J20-transgenic mice have a dramatic reduction of Aβ peptides, fewer and smaller plaques, and more active tissue plasminogen activator associated with plaques. Furthermore, neuroserpin-deficient J20-transgenic mice have near normal performances in the Morris water maze, in contrast to the spatial memory defects seen in J20-transgenic mice. These results support the concept that neuroserpin inhibition of tissue plasminogen activator plays an important role both in the accumulation of brain amyloid plaques and loss of cognitive abilities. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/21689108/Amyloid_beta_levels_are_significantly_reduced_and_spatial_memory_defects_are_rescued_in_a_novel_neuroserpin_deficient_Alzheimer's_disease_transgenic_mouse_model_ L2 - https://doi.org/10.1111/j.1471-4159.2011.07359.x DB - PRIME DP - Unbound Medicine ER -