TY - JOUR
T1 - Cholesterol and Alzheimer's disease - Is there a relation?
AU - Sjögren, Magnus
AU - Mielke, Michelle
AU - Gustafson, Deborah
AU - Zandi, Peter
AU - Skoog, Ingmar
N1 - Funding Information:
Supported by grants from Fredrik och Ingrid Thurings Stiftelse; Martina och Wilhelm Lundgrens Stiftelse; Stiftelsen för Gamla Tjänarinnor; The Swedish Medical Research Council (projects 254181909 and 254181910); and The Johns Hopkins Alzheimer Disease Research Center (P01 AG05146).
PY - 2006/2
Y1 - 2006/2
N2 - The predominating theory on the pathophysiology of Alzheimer's disease (AD) concerns the mis-metabolism of amyloid precursor protein (APP). As a result of this mis-metabolism, there is an increased production of the 42 amino acid form of β-amyloid (Aβ42) that rapidly will form oligomers that initiates a cascade of events leading to the accumulation of amyloid plaques. Commonly recognised as vascular factors, hypertension, hypercholesterolemia and diabetes and the inheritance of the ε4 allele of the APOE gene, are also risk factors for AD. These risks have been found to promote the production of Aβ42. An association between cholesterol and the development of AD was suggested in the early 1990s and ever since, an increasing amount of research has confirmed that there is a link between cholesterol and the development of AD. A high cholesterol levels in mid-life is a risk for AD and statins, i.e., cholesterol-lowering drugs, reduce this risk. Statins may not only inhibit enzymes involved in the endogenous synthesis of cholesterol but also affect enzymes involved in Aβ metabolism, i.e., α-secretase and β-secretase. This normalises the breakdown of APP thereby promoting the non-amyloidogenic pathway. In this review, investigations focusing on cholesterol and Alzheimer's disease are presented.
AB - The predominating theory on the pathophysiology of Alzheimer's disease (AD) concerns the mis-metabolism of amyloid precursor protein (APP). As a result of this mis-metabolism, there is an increased production of the 42 amino acid form of β-amyloid (Aβ42) that rapidly will form oligomers that initiates a cascade of events leading to the accumulation of amyloid plaques. Commonly recognised as vascular factors, hypertension, hypercholesterolemia and diabetes and the inheritance of the ε4 allele of the APOE gene, are also risk factors for AD. These risks have been found to promote the production of Aβ42. An association between cholesterol and the development of AD was suggested in the early 1990s and ever since, an increasing amount of research has confirmed that there is a link between cholesterol and the development of AD. A high cholesterol levels in mid-life is a risk for AD and statins, i.e., cholesterol-lowering drugs, reduce this risk. Statins may not only inhibit enzymes involved in the endogenous synthesis of cholesterol but also affect enzymes involved in Aβ metabolism, i.e., α-secretase and β-secretase. This normalises the breakdown of APP thereby promoting the non-amyloidogenic pathway. In this review, investigations focusing on cholesterol and Alzheimer's disease are presented.
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Cholesterol
KW - Statins
KW - β-Amyloid
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U2 - 10.1016/j.mad.2005.09.020
DO - 10.1016/j.mad.2005.09.020
M3 - Article
C2 - 16332384
AN - SCOPUS:31644446183
SN - 0047-6374
VL - 127
SP - 138
EP - 147
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
IS - 2
ER -