HDL from an Alzheimer's disease perspective

Button, Emily B.; Robert, Jérôme; Caffrey, Tara M.; Fan, Jianjia; Zhao, Wenchen; Wellington, Cheryl L.

doi:10.1097/mol.0000000000000604

Cited by 87 publications

(81 citation statements)

References 181 publications

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“…It has been established that keeping BP in the normal range is an effective strategy for the prevention of primary and secondary dementia. HDL has numerous beneficial functions including preventing amyloid beta aggregation [26] and protecting against amyloid beta-induced inflammation [27]. However, there has been no study to elucidate the correlation between blood pressure and the HDL-C level in the adult population aged 20-80 years.…”

Section: Discussionmentioning

confidence: 99%

Decrease in Serum HDL-C Level Is Associated with Elevation of Blood Pressure: Correlation Analysis from the Korean National Health and Nutrition Examination Survey 2017

Cho

Park

Kim

2020

IJERPH

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A low-serum, high-density lipoproteins-cholesterol (HDL-C) level and high blood pressure (BP) are independent risk factors for cardiovascular disease and dementia. In the present study, in order to find putative correlation between low HDL-C and hypertension, 4552 subjects (20-80 years old) were selected from the Korean National Health And Nutrition Examination Survey 2017 (KNHANES VII-2, n = 2017 men, n = 2535 women). They were classified into four levels of blood pressure, ranging from BP1 (normal, below 120/80 mmHg for systolic BP (SBP)/diastolic BP (DBP), BP2 (prehypertension, 120/80 to 139/89 mmHg), BP3 (hypertension stage 1, 140/90-159/99 mmHg), and BP4 (hypertension stage 2, higher than 160/100 mmHg). Generally, in the total population, a higher SBP level and age were associated with a lower HDL-C in both genders. However, DBP was not associated with age in men. In the total population, Pearson's correlation analysis revealed that SBP (r = −0.188, p < 0.001) and DBP (r = −0.198, p < 0.001) showed negative correlations with percentage of HDL-C in total cholesterol (TC), HDL-C/TC (%). In both genders, HDL-C gradually decreased with age and HDL-C/TC (%) was more accurate in expressing a correlation with BP. Women showed a more distinct decrease in HDL-C with an elevation of BP and age than men. Both elevation of DBP and SBP were associated with a decrease in HDL-C, around 2.3-2.4 mg/dL, between normal range and hypertension 2 stage. Additionally, DBP was significantly associated with HDL-C/TC (%) (men: r = −0.136, p < 0.001; women: r = −0.152, p < 0.001), while HDL-C did not show a significant association with a change in DBP. In conclusion, SBP was positively correlated with age, but DBP did not change significantly with age. The correlation of BP and HDL-C depending on age showed that SBP gradually increased and HDL-C decreased with an increase in age. The percentage of HDL-C in TC was more significantly associated with a change in SBP and DBP in both genders. high total cholesterol (TC) and low high-density lipoproteins-cholesterol (HDL-C) are also independent risk factors of cardiovascular disease and cerebrovascular disease [5]. However, there has been no correlation analysis between change in blood pressure and HDL-C in general population.Hypertension in midlife is also a strong and independent risk factor of Alzheimer's disease and vascular dementia in late-life [6,7], because individuals who develop hypertension earlier in life are likely to be exposed to the deleterious neurological effects of hypertension for many decades. The higher midlife BP was associated with incidence of dementia in late-life [6]. Interestingly, subjects with midlife hypertension and late-life hypotension had a 4.26-fold higher risk of dementia. Blood pressure control is very important to prevent not only cardiovascular disease but also incidence of cognitive impairment and dementia [8]. The positive association of TC and hypertension and inverse associations of HDL-C and future risk of hypertension are well established [9].As...

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Section: Discussionmentioning

confidence: 99%

Decrease in Serum HDL-C Level Is Associated with Elevation of Blood Pressure: Correlation Analysis from the Korean National Health and Nutrition Examination Survey 2017

Cho

Park

Kim

2020

IJERPH

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“…We identified a unique cell type-specific signal between microglia and genetic variants associated with High-density lipoprotein (HDL) cholesterol level (q MAGMA = 0.046) (Figure 2a). Given the role of lipids in AD 15,16 , we asked whether the HDL cholesterol association was related to the association between AD risk and microglia gene expression (Figure 2a). However, conditional analysis suggests distinct genetics underlie the associations of AD and HDL cholesterol levels with microglia ( Supplementary Figure 8).…”

Section: The Single-cell Profiles Of the Substantia Nigra Inform On Tmentioning

confidence: 99%

A human single-cell atlas of the Substantia nigra reveals novel cell-specific pathways associated with the genetic risk of Parkinson’s disease and neuropsychiatric disorders

Agarwal

Sandor

Volpato

et al. 2020

Preprint

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We describe a human single-nuclei transcriptomic atlas for the Substantia nigra (SN), generated by sequencing ~ 17,000 nuclei from matched cortical and SN samples. We show that the common genetic risk for Parkinson's disease (PD) is associated with dopaminergic neuron (DaN)-specific gene expression, including mitochondrial functioning, protein folding and ubiquitination pathways. We identify a distinct cell type association between PD risk and oligodendrocyte-specific gene expression. Unlike Alzheimer's disease (AD), we find no association between PD risk and microglia or astrocytes, suggesting that neuroinflammation plays a less causal role in PD than AD. Beyond PD, we find associations between SN DaNs and GABAergic neuron gene expression patterns with multiple neuropsychiatric disorders. Nevertheless, we find that each neuropsychiatric disorder is associated with a distinct set of genes within that neuron type. This atlas guides our aetiological understanding by associating SN cell type expression profiles with specific disease risk.

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“…A recent meta-analysis reported no signi cant association between HDL-C and AD risk [23]. The protective effects of HDL-C on AD risk have been observed in middle-aged adults, while studies examining patients ≥70 years of age have reported no such association [28]. Furthermore, these observational studies had limited sample sizes of <10,000 [23].…”

Section: Discussionmentioning

confidence: 99%

Associations between vascular risk factors and subsequent Alzheimer’s disease in older adults

Lee

Kim

Lee

et al. 2020

Preprint

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Background: The clinical guidelines related to the primary prevention of Alzheimer’s disease (AD) have focused on the management of vascular risk factors. However, the link between vascular risk factors and AD in older adults remains unclear. This study aimed to determine the association between vascular risk factors and subsequent AD in 178,586 older adults (age: ≥65 years). Methods: Participants were recruited from 2009 through 2010 and followed up for 6 years. We assessed various vascular risk factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], fasting glucose [FG], systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse pressure [PP] and body mass index [BMI]) and their association with AD incidence, categorizing each vascular factor using current clinical guidelines. Results: AD was observed in 6.0% of participants at follow-up. All lipid profiles (TC, LDL-C, HDL-C, TG) were positively associated with the risk of AD. SBP and PP were in negative associations with AD, and DBP was positively associated with AD. BMI exhibited a negative association with AD incidence. We found no significant association between FG and AD risk. The sex difference was observed to have effects on vascular risk factors.Conclusions: In this study, we comprehensively investigated the association between eight vascular risk factors and the risk of incident AD. Our findings suggest that multiple vascular risk factors are related to the development of AD in older adults. These results can help inform future guidelines for reducing AD risk.

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HDL from an Alzheimer's disease perspective

Cited by 87 publications

References 181 publications

Decrease in Serum HDL-C Level Is Associated with Elevation of Blood Pressure: Correlation Analysis from the Korean National Health and Nutrition Examination Survey 2017

Decrease in Serum HDL-C Level Is Associated with Elevation of Blood Pressure: Correlation Analysis from the Korean National Health and Nutrition Examination Survey 2017

A human single-cell atlas of the Substantia nigra reveals novel cell-specific pathways associated with the genetic risk of Parkinson’s disease and neuropsychiatric disorders

Associations between vascular risk factors and subsequent Alzheimer’s disease in older adults

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