The Effect of Simvastatin Treatment on the Amyloid Precursor Protein and Brain Cholesterol Metabolism in Patients with Alzheimer’s Disease

Vol. 19, No. 5-6, 2005

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Original Research Article

The Effect of Simvastatin Treatment on the Amyloid Precursor Protein and Brain Cholesterol Metabolism in Patients with Alzheimer's Disease
K. Höglund^a, K.M. Thelen^d, S. Syversen^b, M. Sjögren^c, K. von Bergmann^d, A. Wallin^b, E. Vanmechelen^e, H. Vanderstichele^e, D. Lütjohann^d, K. Blennow^a

^aSection of Experimental Neurochemistry, and
^bSection of Psychiatry, Institute of Clinical Neuroscience, Göteborg University, Göteborg, and
^cDepartment of Neuropsychiatry, Sahlgrenska University Hospital, Mölndal/Göteborg, Sweden;
^dDepartment of Clinical Pharmacology, University of Bonn, Bonn, Germany;
^eInnogenetics NV, Zwijnaarde, Belgium

Address of Corresponding Author

Dement Geriatr Cogn Disord 2005;19:256-265 (DOI: 10.1159/000084550)

Key Words

Alzheimer's disease
-Amyloid
Amyloid precursor protein
Cholesterol metabolism
Central nervous system
Statins
24S-Hydroxycholesterol

Abstract

During the last years, several clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in Alzheimer's disease (AD) in humans. We present an open biochemical study where 19 patients with AD have been treated with simvastatin (20 mg/day) for 12 months. The aim was to further investigate the effect of simvastatin treatment on cerebrospinal fluid (CSF) biomarkers of APP processing, AD biomarkers as total tau and tau phosphorylated at threonine 181, brain cholesterol metabolism as well as on cognitive decline in patients with AD. Despite biochemical data suggesting that treatment with 20 mg/day of simvastatin for 12 months does affect the brain cholesterol metabolism, we did not find any change in CSF or plasma levels of beta -amyloid (A beta )_1-42. However, by analysis of APP isoforms, we found that statin treatment may favor the nonamyloidogenic pathway of APP processing. The relevance and mechanism between statin treatment and AD has to be further elucidated by using statins of different lipophility in different dosages over a longer period of time.

Author Contacts

Kina Höglund, MSc
Institute of Clinical Neuroscience
Section of Laboratory Neuroscience, Neurolabb, SU/Mölndal
SE-431 80 Mölndal (Sweden)
Tel. +46 31 343 23 77, Fax +46 31 343 24 26, E-Mail kina.hoglund@neuro.gu.se

Article Information

Accepted: September 19, 2004
Published online: March 21, 2005
Number of Print Pages : 10
Number of Figures : 1, Number of Tables : 3, Number of References : 53

Medline Abstract (ID 15785028)

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