The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer's disease
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The effect of simvastatin treatment on the amyloid precursor protein and brain cholesterol metabolism in patients with Alzheimer's disease. / Hoglund, K; Thelen, K M; Syversen, S; Sjogren, M; von Bergmann, K; Wallin, A; Vanmechelen, E; Vanderstichele, H; Lutjohann, D; Blennow, K.
I: Dementia and Geriatric Cognitive Disorders, Bind 19, Nr. 5-6, 2005, s. 256-65.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
VL - 19
SP - 256
EP - 265
JO - Dementia and Geriatric Cognitive Disorders
JF - Dementia and Geriatric Cognitive Disorders
SN - 1420-8008
IS - 5-6
ER -
ID: 189705483