Effect of statins on Alzheimer's disease biomarkers in cerebrospinal fluid.
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-beta (Abeta) 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, Abeta42, Abeta40, soluble amyloid beta protein precursor (sAbetaPP) alpha or beta, 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.
Riekse
Robert G
RG
Department of Medicine, Division of Geriatric Medicine, University of Washington School of Medicine, and VA Puget Sound Health Care System, Seattle, WA 98108, USA.
Li
Ge
G
Petrie
Eric C
EC
Leverenz
James B
JB
Vavrek
Darcy
D
Vuletic
Simona
S
Albers
John J
JJ
Montine
Thomas J
TJ
Lee
Virginia M-Y
VM
Lee
Michael
M
Seubert
Peter
P
Galasko
Douglas
D
Schellenberg
Gerard D
GD
Hazzard
William R
WR
Peskind
Elaine R
ER
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D028441:F2-Isoprostanes / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D017035:Pravastatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019821:Simvastatin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008078:Cholesterol, LDL; D028441:F2-Isoprostanes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014280:Triglycerides; C500436:amyloid beta-peptide (5-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D002784:Cholesterol; D019821:Simvastatin; D017035:Pravastatin