Serum levels of proteins involved in amyloid‐β clearance are related to cognitive decline and neuroimaging changes in mild cognitive impairment

Liu, Shan; Suzuki, Hideaki; Ito, Hitomi; Korenaga, Tatsumi; Akatsu, Hiroyasu; Meno, Kohji; Uchida, Keiji

doi:10.1016/j.dadm.2018.11.003

Cited by 26 publications

(26 citation statements)

References 38 publications

(45 reference statements)

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“…Circulating apoA-I levels are negatively associated with risk of future dementia in many [72,73,74 ▪▪ ] but not all [77–80] studies. Furthermore, although a panel including serum apoA-I was shown to have high sensitivity and specificity for MCI [177,178], there were no HDL-associated protein hits in a nontargeted proteomic analysis employed to develop a multiprotein Alzheimer's disease biomarker panel [179]. Early work investigating HDL-associated protein levels and cerebrovascular dysfunction found that serum apoA-I levels are significantly lower in Alzheimer's disease, MCI, and control subjects with severe CBF impairments [178].…”

Section: Hdl As a Potential Predictive Biomarker For Vascular Comprommentioning

confidence: 99%

“…Furthermore, although a panel including serum apoA-I was shown to have high sensitivity and specificity for MCI [177,178], there were no HDL-associated protein hits in a nontargeted proteomic analysis employed to develop a multiprotein Alzheimer's disease biomarker panel [179]. Early work investigating HDL-associated protein levels and cerebrovascular dysfunction found that serum apoA-I levels are significantly lower in Alzheimer's disease, MCI, and control subjects with severe CBF impairments [178]. Other studies found that the levels of HDL particles containing apoE and lacking apoJ predict greater WMH volume in normal and MCI subjects [180], and that plasma apoJ levels are higher in subjects with CAA-related intracerebral hemorrhages compared with Alzheimer's disease subjects [68].…”

Section: Hdl As a Potential Predictive Biomarker For Vascular Comprommentioning

confidence: 99%

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HDL from an Alzheimer's disease perspective

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Robert

Caffrey

et al. 2019

Current Opinion in Lipidology

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Purpose of review We review current knowledge regarding HDL and Alzheimer's disease, focusing on HDL's vasoprotective functions and potential as a biomarker and therapeutic target for the vascular contributions of Alzheimer's disease. Recent findings Many epidemiological studies have observed that circulating HDL levels associate with decreased Alzheimer's disease risk. However, it is now understood that the functions of HDL may be more informative than levels of HDL cholesterol (HDL-C). Animal model studies demonstrate that HDL protects against memory deficits, neuroinflammation, and cerebral amyloid angiopathy (CAA). In-vitro studies using state-of-the-art 3D models of the human blood–brain barrier (BBB) confirm that HDL reduces vascular Aβ accumulation and attenuates Aβ-induced endothelial inflammation. Although HDL-based therapeutics have not been tested in clinical trials for Alzheimer's disease , several HDL formulations are in advanced phase clinical trials for coronary artery disease and atherosclerosis and could be leveraged toward Alzheimer's disease . Summary Evidence from human studies, animal models, and bioengineered arteries supports the hypothesis that HDL protects against cerebrovascular dysfunction in Alzheimer's disease. Assays of HDL functions relevant to Alzheimer's disease may be desirable biomarkers of cerebrovascular health. HDL-based therapeutics may also be of interest for Alzheimer's disease, using stand-alone or combination therapy approaches.

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Section: Hdl As a Potential Predictive Biomarker For Vascular Comprommentioning

confidence: 99%

Section: Hdl As a Potential Predictive Biomarker For Vascular Comprommentioning

confidence: 99%

HDL from an Alzheimer's disease perspective

Button

Robert

Caffrey

et al. 2019

Current Opinion in Lipidology

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“…However, these methods may not only be invasive but also unaffordable to some patients. Blood lipid profiles as biomarkers may be more accessible, affordable, and less invasive modalities to detect and diagnose AD (Zarrouk et al, 2018;Liu et al, 2019). Some lipids extracted from peripheral blood have been validated to predict development to either amnestic mild cognitive impairment (aMCI) or AD with over 90% accuracy (Mapstone et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study

Tang

Wang

Yang

et al. 2020

Front. Aging Neurosci.

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Objectives: Blood lipid profiles have been ambiguously reported as biomarkers of AD in recent years. This study was conducted to evaluate the correlation between blood lipid levels and AD in later-life and to explore the effectiveness and reliability of blood lipid profiles as biomarkers of AD. Methods: Database searching was conducted using PubMed, the Cochrane Library, EMBASE, and Medline. This study was designed following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria. Review Manager 5.3 (RevMan 5.3) software was adopted to perform meta-analysis evaluating the standard mean difference (SMD) with its 95% confidence intervals (CI). Results: A total of 5,286 participants were enrolled from 27 case-control studies in this meta-analysis. The pooled results demonstrated that total cholesterol (TC) level was significantly associated with AD in late-life (SMD = 0.17, 95% CI: [0.01, 0.32], P = 0.03), especially in the subgroup under 70 years old (SMD: 0.45, 95% CI: [0.11, 0.79], P = 0.01) and the subgroup of Western population (SMD: 0.29, 95% CI: [0.04, 0.53], P = 0.02). In the subgroup under 70 years old, the high-density lipoprotein cholesterol (HDL-C) level (SMD = −0.50, 95% CI: [−0.76, −0.25], P = 0.0001) and the low-density lipoprotein cholesterol (LDL-C) level (SMD = 0.59, 95% CI: [0.02, 1.16], P = 0.04) in the AD group were significantly lower and higher than in the control group, respectively. In the subgroup with a sample size larger than 100 subjects, the LDL-C level was significantly higher in AD patients than in the control elderly group (SMD = 0.31, 95% CI: [0.05, 0.56], P = 0.02). There was no significant association between triglyceride (TG) levels and AD in later-life (SMD = −0.00, 95% CI: [−0.12, 0.12], P = 1.00). Tang et al. Association Between Lipids and AD Conclusion: TC can be a new predictive biomarker of AD or cognitive decline in later-life. Increased TC levels are found to be associated with an elevated risk of AD. Decreased HDL-C levels and increased LDL-C levels may relate to an elevated risk of AD in subjects aged 60-70. Further comprehensive researches will be necessary in the future.

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“…Frequently, cardiovascular vascular disease (CVD) is associated with the coincidence of MCI and Alzheimer’s disease (AD) [8], even though the pathologic link between CVD and AD remain to be elucidated. As well as prevention of CVD, raising the HDL-C level is a good strategy to attenuate dementia, because HDL can inhibit the aggregation of beta-amyloid (Aβ) and promote the removal of amyloid [9]. Furthermore, HDL reduces the level of vascular Aβ accumulation and attenuates Aβ-induced endothelial inflammation [10,11].…”

Section: Introductionmentioning

confidence: 99%

Decrease in HDL-C is Associated with Age and Household Income in Adults from the Korean National Health and Nutrition Examination Survey 2017: Correlation Analysis of Low HDL-C and Poverty

Cho

Park

Kim

et al. 2019

IJERPH

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A low serum high-density lipoproteins-cholesterol (HDL-C) level is a risk factor of cardiovascular disease and dementia. On the other hand, no study has elucidated the correlation between household income and the HDL-C level in the adult population. In the present study, 5535 subjects (20–80 year-old individuals) were selected from the Korean national health and nutrition examination survey 2017 (KNHANES VII-2, n = 2469 men, n = 3066 women). They were classified into five levels of household income grades ranging from one (the lowest) to five (the highest). They were also classified according to the HDL-C level: category 1 (<40 mg/dL, n = 943), category 2 (40–49 mg/dL, n = 1764), category 3 (50–59 mg/dL, n = 1572), category 4 (60–69 mg/dL, n = 820), and category 5 (≥70 mg/dL, n = 436). Generally, in both genders, a higher HDL-C level is associated with a larger percentage of income grades 4 and 5. Moreover, the lowest HDL-C group showed the largest percentage of income grade 1. In both groups, a significant increase in the average income grade was associated with a concomitant increase in the HDL-C level (men, p = 0.03, women, p < 0.001). In the low HDL-C category, a lower income grade is associated directly with a lower HDL-C level, which suggests that poverty is associated directly with a low HDL-C. Women showed a 3.3-fold higher incidence of dementia than men did at later-life. The sharp decrease in HDL-C in the female group older than 50 was accompanied by a dramatic increase in the incidence of dementia. However, the male group showed a relatively mild decrease in the HDL-C level after mid-life and weak elevation in the incidence of dementia. In conclusion, in both genders, the lower income group showed a larger prevalence of low-HDL-C levels. The decrease in HDL-C after middle age was strongly associated with the considerable increase in dementia in later-life.

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Serum levels of proteins involved in amyloid‐β clearance are related to cognitive decline and neuroimaging changes in mild cognitive impairment

Cited by 26 publications

References 38 publications

HDL from an Alzheimer's disease perspective

HDL from an Alzheimer's disease perspective

Revealing a Novel Landscape of the Association Between Blood Lipid Levels and Alzheimer's Disease: A Meta-Analysis of a Case-Control Study

Decrease in HDL-C is Associated with Age and Household Income in Adults from the Korean National Health and Nutrition Examination Survey 2017: Correlation Analysis of Low HDL-C and Poverty

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