The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer's disease

TY - JOUR

T1 - The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer's disease

AU - Hoglund, K

AU - Thelen, K M

AU - Syversen, S

AU - Sjogren, M

AU - von Bergmann, K

AU - Wallin, A

AU - Vanmechelen, E

AU - Vanderstichele, H

AU - Lutjohann, D

AU - Blennow, K

PY - 2005

Y1 - 2005

N2 - 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 (Abeta)(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.

AB - 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 (Abeta)(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.

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Amyloid beta-Protein Precursor

KW - Anticholesteremic Agents

KW - Biomarkers

KW - Brain Chemistry

KW - Cholesterol

KW - Cognition

KW - Cognition Disorders

KW - Female

KW - Humans

KW - Lipids

KW - Male

KW - Phosphorylation

KW - Simvastatin

KW - Sterols

KW - tau Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1159/000084550

DO - 10.1159/000084550

M3 - Journal article

C2 - 15785028

SN - 1420-8008

VL - 19

SP - 256

EP - 265

JO - Dementia and Geriatric Cognitive Disorders

JF - Dementia and Geriatric Cognitive Disorders

IS - 5-6

ER -