Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid

Robert G. Riekse; Ge Li; Eric C. Petrie; James B. Leverenz; Darcy Vavrek; Simona Vuletic; John J. Albers; Thomas J. Montine; Virginia M.Y. Lee; Michael Lee; Peter Seubert; Douglas Galasko; Gerard D. Schellenberg; William R. Hazzard; Elaine R. Peskind

doi:10.3233/JAD-2006-10408

Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid

Robert G. Riekse, Ge Li, Eric C. Petrie, James B. Leverenz, Darcy Vavrek, Simona Vuletic, John J. Albers, Thomas J. Montine, Virginia M.Y. Lee, Michael Lee, Peter Seubert, Douglas Galasko, Gerard D. Schellenberg, William R. Hazzard, Elaine R. Peskind

Neuroscience

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

Abstract

Background: Treatment with HMG-CoA reductase inhibitors ("statins") has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-β (Aβ) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system (CNS). Methods: We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n = 10) at 40 mg/day or pravastatin (a CNS impermeant statin; n = 13) at 80 mg/day in hypercholesterolemic subjects without dementia. Results: Simvastatin, but not pravastatin, reduced CSF levels of phospho-tau-181 (p-tau₁₈₁) in all subjects. There were no differences in CSF levels of total tau, Aβ₄₂, Aβ₄₀, soluble amyloid β protein precursor (sAβPP) α or β, or F₂- isoprostanes. Conclusions: Statins may modulate the phosphorylation of tau in humans and this effect may depend on the CNS availability of the statin. These results suggest another mechanism by which statins may act to reduce the risk of AD.

Original language	English (US)
Pages (from-to)	399-406
Number of pages	8
Journal	Journal of Alzheimer's Disease
Volume	10
Issue number	4
DOIs	https://doi.org/10.3233/JAD-2006-10408
State	Published - 2006

Keywords

Alzheimer's disease
CSF
Clinical trial
Statins
Tau

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3233/JAD-2006-10408

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Riekse, R. G., Li, G., Petrie, E. C., Leverenz, J. B., Vavrek, D., Vuletic, S., Albers, J. J., Montine, T. J., Lee, V. M. Y., Lee, M., Seubert, P., Galasko, D., Schellenberg, G. D., Hazzard, W. R., & Peskind, E. R. (2006). Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid. Journal of Alzheimer's Disease, 10(4), 399-406. https://doi.org/10.3233/JAD-2006-10408

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abstract = "Background: Treatment with HMG-CoA reductase inhibitors ({"}statins{"}) has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-β (Aβ) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system (CNS). Methods: We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n = 10) at 40 mg/day or pravastatin (a CNS impermeant statin; n = 13) at 80 mg/day in hypercholesterolemic subjects without dementia. Results: Simvastatin, but not pravastatin, reduced CSF levels of phospho-tau-181 (p-tau181) in all subjects. There were no differences in CSF levels of total tau, Aβ42, Aβ40, soluble amyloid β protein precursor (sAβPP) α or β, or F2- isoprostanes. Conclusions: Statins may modulate the phosphorylation of tau in humans and this effect may depend on the CNS availability of the statin. These results suggest another mechanism by which statins may act to reduce the risk of AD.",

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doi = "10.3233/JAD-2006-10408",

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T1 - Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid

AU - Riekse, Robert G.

AU - Li, Ge

AU - Petrie, Eric C.

AU - Leverenz, James B.

AU - Vavrek, Darcy

AU - Vuletic, Simona

AU - Albers, John J.

AU - Montine, Thomas J.

AU - Lee, Virginia M.Y.

AU - Lee, Michael

AU - Seubert, Peter

AU - Galasko, Douglas

AU - Schellenberg, Gerard D.

AU - Hazzard, William R.

AU - Peskind, Elaine R.

PY - 2006

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N2 - Background: Treatment with HMG-CoA reductase inhibitors ("statins") has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-β (Aβ) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system (CNS). Methods: We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n = 10) at 40 mg/day or pravastatin (a CNS impermeant statin; n = 13) at 80 mg/day in hypercholesterolemic subjects without dementia. Results: Simvastatin, but not pravastatin, reduced CSF levels of phospho-tau-181 (p-tau181) in all subjects. There were no differences in CSF levels of total tau, Aβ42, Aβ40, soluble amyloid β protein precursor (sAβPP) α or β, or F2- isoprostanes. Conclusions: Statins may modulate the phosphorylation of tau in humans and this effect may depend on the CNS availability of the statin. These results suggest another mechanism by which statins may act to reduce the risk of AD.

AB - Background: Treatment with HMG-CoA reductase inhibitors ("statins") has been variably associated with a reduced risk of Alzheimer's disease (AD) in epidemiologic studies and reduced amyloid-β (Aβ) deposition in animal models of AD. Putative neuroprotective effects of statins may vary in relation to their ability to penetrate into the central nervous system (CNS). Methods: We measured levels of cerebrospinal fluid (CSF) AD biomarkers following 14 weeks of treatment with simvastatin (a CNS permeant statin; n = 10) at 40 mg/day or pravastatin (a CNS impermeant statin; n = 13) at 80 mg/day in hypercholesterolemic subjects without dementia. Results: Simvastatin, but not pravastatin, reduced CSF levels of phospho-tau-181 (p-tau181) in all subjects. There were no differences in CSF levels of total tau, Aβ42, Aβ40, soluble amyloid β protein precursor (sAβPP) α or β, or F2- isoprostanes. Conclusions: Statins may modulate the phosphorylation of tau in humans and this effect may depend on the CNS availability of the statin. These results suggest another mechanism by which statins may act to reduce the risk of AD.

KW - Alzheimer's disease

KW - CSF

KW - Clinical trial

KW - Statins

KW - Tau

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JO - Journal of Alzheimer's Disease

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SN - 1387-2877

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ER -

Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid

Abstract

Keywords

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