Plasma Aβ42 correlates positively with increased body fat in healthy individuals

Balakrishnan, Kelvin; Verdile, Giuseppe; Mehta, Pankaj; Beilby, John; Nolan, David; Galvão, Daniel A.; Newton, Robert U.; Gandy, Samuel E.; Martins, Ralph N.

doi:10.3233/jad-2005-8305

Cited by 76 publications

(58 citation statements)

References 80 publications

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“…76 Thus RAGE plays a direct and indirect role in AD pathogenesis, in particular, the apparent inverse relationship between sRAGE and cholesterol may add yet another modulatory effect on Ab metabolism as cholesterol is a known mediator of inflammation and APP processing. [93][94][95][96][97][98][99][100][101][102][103][104] Efflux of Ab: LRP-1/Ab interactions at BBB LRP-1 is a multi-ligand lipoprotein receptor involved in the mediation of endocytosis or activation of signalling molecules for a diverse range of secreted and membrane-bound ligands. Receptor activating protein (RAP) is a 39 kDa chaperone protein that binds to LRP-1 and regulates its tertiary structure.…”

Section: Influx Of Ab Rage/ab Interactions At Bbbmentioning

confidence: 99%

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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Currently, the 'amyloid hypothesis' is the most widely accepted explanation for the pathogenesis of Alzheimer's disease (AD). According to this hypothesis, altered metabolism of the amyloid-b (Ab) peptide is central to the pathological cascade involved in the pathogenesis of AD. Although Ab is produced by almost every cell in the body, a physiological function for the peptide has not been determined, and the pathways by which Ab leads to cognitive dysfunction and cell death are unclear. Numerous therapeutic approaches that target the production, toxicity and removal of Ab are being developed worldwide. Although therapeutic treatment for AD may be imminent, the value and effectiveness of such treatment are largely dependent on early diagnosis of the disease. This review summarizes current knowledge of Ab clearance, transport and degradation, and evaluates the use of such information in the development of diagnostic tools. The conflicting results of plasma Ab ELISAs are discussed, as are the more promising results of Ab imaging by positron emission tomography. Current knowledge of Ab-binding proteins and Ab-degrading enzymes is analysed in the context of a potential therapy for AD. Transport across the blood-brain barrier by the receptor for advanced glycation end products and efflux via the multi-ligand lipoprotein receptor LRP-1 is also reviewed. Enhancing clearance and degradation of Ab remains an attractive therapeutic strategy, and improved understanding of Ab clearance may lead to advances in diagnostics and interventions designed to prevent or delay the onset of AD.

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Section: Influx Of Ab Rage/ab Interactions At Bbbmentioning

confidence: 99%

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

et al. 2008

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“…We found a significant positive correlation of HDL levels with Aβ 1-42 levels among statin nonusers. Similarly, a previous study evaluating plasma Aβ 1-42 among 18 healthy individuals found a correlation between HDL and Aβ (35). However, Mayeux and colleagues reported an association of HDL with Aβ 1-40 instead (2).…”

Section: H I G H a β I N R E L A T I V E S O F A D P A T I E N T Smentioning

confidence: 81%

High Serum Aβ and Vascular Risk Factors in First-Degree Relatives of Alzheimer’s Disease Patients

Abdullah

Luis

Paris

et al. 2009

Mol Med

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The main objective of this study was to determine whether elevated blood β-amyloid (Aβ) levels among the first-degree relatives of patients with Alzheimer's Disease (AD) are associated with vascular risk factors of AD. Serum Aβ was measured in samples from 197 cognitively normal first-degree relatives of patients with AD-like dementia. Study participants were recruited as part of an ancillary study of the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT subpopulation). The ADAPT subpopulation was found to be similar in age, sex, and ethnicity to another cognitively normal cohort (n = 98). Using cross-sectional analyses, we examined the association of Aβ with blood pressure, lipid levels, apolipoprotein E genotypes, and the use of prescribed medication to treat vascular risk factors in the ADAPT subpopulation. Aβ 1-40 was positively associated with age, use of antihypertensives, and serum creatinine, and we observed a marginal negative interaction on Aβ 1-40 associated with systolic blood pressure and use of antihypertensives. Serum Aβ 1-42 was associated with statin use and a positive correlation of Aβ 1-42 with HDL was observed among statin nonusers. These findings suggest that high Aβ in the periphery among the family history-enriched cohorts may be due to enrichment of vascular risk factors and may reflect presymptomatic AD pathology. It remains to be determined whether the association of Aβ with medications used for treating vascular risk factors indicates prevention of AD. Longitudinal evaluation of blood Aβ in this cohort will provide a better understanding of the significance of this association in AD etiology.

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“…[115][116][117] Obese men have been found to have lower cognitive function when compared with non-obese normotensive men, 115 and in an 18 year follow-up study in overweight women, a high risk for dementia (particularly AD) was found in these women relative to controls. 116 In our own recent studies, we have observed a strong positive correlation between body fat and blood Ab1À42 levels in cognitively normal individuals, 118 and in a recent longitudinal study of 1149 individuals, mid-life obesity was found to be a significant risk factor for AD later in life. 119 This association has now also been linked to hyperinsulinemia: insulin infusion (inducing temporary hyperinsulinemia) increases blood plasma Ab1À42 levels in cognitively normal individuals who are offspring of AD patients: and the magnitude of Ab1À42 increase is greater in subjects with increased abdominal body fat.…”

Section: Statins and Admentioning

confidence: 85%

Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease

et al. 2006

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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 e4 (APOE e4) alleles further increases the risk or severity of many of these conditions, including AD. ApoE has roles in cholesterol metabolism and Ab clearance, both of which are thought to be significant in AD pathogenesis. The apparent inadequacies of ApoE e4 in these roles may explain the increased risk of AD in subjects carrying one or more APOE e4 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.

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Plasma Aβ42 correlates positively with increased body fat in healthy individuals

Cited by 76 publications

References 80 publications

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests

High Serum Aβ and Vascular Risk Factors in First-Degree Relatives of Alzheimer’s Disease Patients

Apolipoprotein E, cholesterol metabolism, diabetes, and the convergence of risk factors for Alzheimer's disease and cardiovascular disease

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