TY - JOUR

T1 - Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer’s disease and cardiovascular disease.

AU - Martins, I. J.

AU - Hone, E.

AU - Foster, J. K.

AU - Sünram-Lea, S. I.

AU - Gnjec, A.

AU - Nolan, D.

AU - Gandy, S. E.

AU - Martins, R. N.

PY - 2006/8

Y1 - 2006/8

N2 - High fat diets and sedentary lifestyles are becoming major concerns for Western countries. They have led to a growing incidence of obesity, dyslipidemia, high blood pressure, and a condition known as the insulin-resistance syndrome or metabolic syndrome. These health conditions are well known to develop along with, or be precursors to atherosclerosis, cardiovascular disease, and diabetes. Recent studies have found that most of these disorders can also be linked to an increased risk of Alzheimer's disease (AD). To complicate matters, possession of one or more apolipoprotein E 4 (APOE 4) alleles further increases the risk or severity of many of these conditions, including AD. ApoE has roles in cholesterol metabolism and A clearance, both of which are thought to be significant in AD pathogenesis. The apparent inadequacies of ApoE 4 in these roles may explain the increased risk of AD in subjects carrying one or more APOE 4 alleles. This review describes some of the physiological and biochemical changes that the above conditions cause, and how they are related to the risk of AD. A diversity of topics is covered, including cholesterol metabolism, glucose regulation, diabetes, insulin, ApoE function, amyloid precursor protein metabolism, and in particular their relevance to AD. It can be seen that abnormal lipid, cholesterol and glucose metabolism are consistently indicated as central in the pathophysiology, and possibly the pathogenesis of AD. As diagnosis of mild cognitive impairment and early AD are becoming more reliable, and as evidence is accumulating that health conditions such as diabetes, obesity, and coronary artery disease are risk factors for AD, appropriate changes to diets and lifestyles will likely reduce AD risk, and also improve the prognosis for people already suffering from such conditions.

AB - High fat diets and sedentary lifestyles are becoming major concerns for Western countries. They have led to a growing incidence of obesity, dyslipidemia, high blood pressure, and a condition known as the insulin-resistance syndrome or metabolic syndrome. These health conditions are well known to develop along with, or be precursors to atherosclerosis, cardiovascular disease, and diabetes. Recent studies have found that most of these disorders can also be linked to an increased risk of Alzheimer's disease (AD). To complicate matters, possession of one or more apolipoprotein E 4 (APOE 4) alleles further increases the risk or severity of many of these conditions, including AD. ApoE has roles in cholesterol metabolism and A clearance, both of which are thought to be significant in AD pathogenesis. The apparent inadequacies of ApoE 4 in these roles may explain the increased risk of AD in subjects carrying one or more APOE 4 alleles. This review describes some of the physiological and biochemical changes that the above conditions cause, and how they are related to the risk of AD. A diversity of topics is covered, including cholesterol metabolism, glucose regulation, diabetes, insulin, ApoE function, amyloid precursor protein metabolism, and in particular their relevance to AD. It can be seen that abnormal lipid, cholesterol and glucose metabolism are consistently indicated as central in the pathophysiology, and possibly the pathogenesis of AD. As diagnosis of mild cognitive impairment and early AD are becoming more reliable, and as evidence is accumulating that health conditions such as diabetes, obesity, and coronary artery disease are risk factors for AD, appropriate changes to diets and lifestyles will likely reduce AD risk, and also improve the prognosis for people already suffering from such conditions.

KW - cholesterol

KW - diabetes

KW - obesity

KW - -amyloid

KW - Alzheimer's disease

KW - apoE

KW - glucose

KW - insulin

KW - cognition

KW - statin

KW - memory

KW - dementia

U2 - 10.1038/sj.mp.4001854

DO - 10.1038/sj.mp.4001854

M3 - Journal article

VL - 11

SP - 721

EP - 736

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 8

ER -