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MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice

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MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice. / Hawkes, Cheryl A.; Shaw, James E.; Brown, Mary et al.
In: Neurodegenerative Diseases, Vol. 13, No. 1, 01.12.2013, p. 17-23.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Hawkes, CA, Shaw, JE, Brown, M, Sampson, AP, McLaurin, J & Carare, RO 2013, 'MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice', Neurodegenerative Diseases, vol. 13, no. 1, pp. 17-23. https://doi.org/10.1159/000351096

APA

Hawkes, C. A., Shaw, J. E., Brown, M., Sampson, A. P., McLaurin, J., & Carare, R. O. (2013). MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice. Neurodegenerative Diseases, 13(1), 17-23. https://doi.org/10.1159/000351096

Vancouver

Hawkes CA, Shaw JE, Brown M, Sampson AP, McLaurin J, Carare RO. MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice. Neurodegenerative Diseases. 2013 Dec 1;13(1):17-23. doi: 10.1159/000351096

Author

Hawkes, Cheryl A. ; Shaw, James E. ; Brown, Mary et al. / MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice. In: Neurodegenerative Diseases. 2013 ; Vol. 13, No. 1. pp. 17-23.

Bibtex

@article{3ea7bc6dd5674ad3b7eb9b22f6c8b4bc,
title = "MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice",
abstract = "Background: Deposition of amyloid-β (Aβ) in blood vessel walls as cerebral amyloid angiopathy (CAA) is observed in the majority of Alzheimer's disease (AD) brains. Inhibition of the 5-lipoxygenase (5-LOX) pathway has recently been suggested to play a role in reducing parenchymal Aβ deposition. However, products of the 5-LOX pathway also activate the peroxisome proliferator-activated receptor (PPAR) family, which promotes clearance of Aβ from the brain. Methods: In the present study, we investigated the effect of MK886, a 5-LOX-activating protein (FLAP) inhibitor and PPARα antagonist, on CAA severity in TgCRND8 mice overexpressing the human Swedish and Indiana amyloid precursor protein mutations. Results: We found that MK886 significantly reduced brain levels of nicastrin and PPARα, but did not affect levels of β-secretase, apolipoprotein E or low-density lipoprotein receptor-related protein-1. CAA severity and parenchymal plaque load was significantly decreased in both the cortex and hippocampus of mice treated with MK886 compared to control mice. Conclusion: These data suggest that 5-LOX and FLAP inhibitors may be useful in the treatment of CAA and AD.",
keywords = "Cerebral amyloid angiopathy, Leukotriene inhibitor, Peroxisome proliferator-activated receptor",
author = "Hawkes, {Cheryl A.} and Shaw, {James E.} and Mary Brown and Sampson, {Anthony P.} and Joanne McLaurin and Carare, {Roxana O.}",
year = "2013",
month = dec,
day = "1",
doi = "10.1159/000351096",
language = "English",
volume = "13",
pages = "17--23",
journal = "Neurodegenerative Diseases",
issn = "1660-2854",
publisher = "S. Karger AG",
number = "1",

}

RIS

TY - JOUR

T1 - MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice

AU - Hawkes, Cheryl A.

AU - Shaw, James E.

AU - Brown, Mary

AU - Sampson, Anthony P.

AU - McLaurin, Joanne

AU - Carare, Roxana O.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Background: Deposition of amyloid-β (Aβ) in blood vessel walls as cerebral amyloid angiopathy (CAA) is observed in the majority of Alzheimer's disease (AD) brains. Inhibition of the 5-lipoxygenase (5-LOX) pathway has recently been suggested to play a role in reducing parenchymal Aβ deposition. However, products of the 5-LOX pathway also activate the peroxisome proliferator-activated receptor (PPAR) family, which promotes clearance of Aβ from the brain. Methods: In the present study, we investigated the effect of MK886, a 5-LOX-activating protein (FLAP) inhibitor and PPARα antagonist, on CAA severity in TgCRND8 mice overexpressing the human Swedish and Indiana amyloid precursor protein mutations. Results: We found that MK886 significantly reduced brain levels of nicastrin and PPARα, but did not affect levels of β-secretase, apolipoprotein E or low-density lipoprotein receptor-related protein-1. CAA severity and parenchymal plaque load was significantly decreased in both the cortex and hippocampus of mice treated with MK886 compared to control mice. Conclusion: These data suggest that 5-LOX and FLAP inhibitors may be useful in the treatment of CAA and AD.

AB - Background: Deposition of amyloid-β (Aβ) in blood vessel walls as cerebral amyloid angiopathy (CAA) is observed in the majority of Alzheimer's disease (AD) brains. Inhibition of the 5-lipoxygenase (5-LOX) pathway has recently been suggested to play a role in reducing parenchymal Aβ deposition. However, products of the 5-LOX pathway also activate the peroxisome proliferator-activated receptor (PPAR) family, which promotes clearance of Aβ from the brain. Methods: In the present study, we investigated the effect of MK886, a 5-LOX-activating protein (FLAP) inhibitor and PPARα antagonist, on CAA severity in TgCRND8 mice overexpressing the human Swedish and Indiana amyloid precursor protein mutations. Results: We found that MK886 significantly reduced brain levels of nicastrin and PPARα, but did not affect levels of β-secretase, apolipoprotein E or low-density lipoprotein receptor-related protein-1. CAA severity and parenchymal plaque load was significantly decreased in both the cortex and hippocampus of mice treated with MK886 compared to control mice. Conclusion: These data suggest that 5-LOX and FLAP inhibitors may be useful in the treatment of CAA and AD.

KW - Cerebral amyloid angiopathy

KW - Leukotriene inhibitor

KW - Peroxisome proliferator-activated receptor

U2 - 10.1159/000351096

DO - 10.1159/000351096

M3 - Journal article

C2 - 24021653

AN - SCOPUS:84891099134

VL - 13

SP - 17

EP - 23

JO - Neurodegenerative Diseases

JF - Neurodegenerative Diseases

SN - 1660-2854

IS - 1

ER -