Joint Effect of Hypertension and APOE Genotype on CSF Biomarkers for Alzheimer's Disease

Background: The previous studies have identified several genes in relation to Alzheimer’s disease (AD), such as ABCA7, CR1, etc. A few studies have explored the association between the common variants, mainly in the non-coding regions of these genes, and cerebrospinal fluid (CSF) biomarkers. Fewer studies target the variants in the coding regions. Objective: To illustrate the association between the common variants within or adjacent to the coding regions of AD susceptible genes and CSF biomarkers in AD patients. Methods: 75 sporadic probable AD patients were extracted from the dementia cohort of Peking Union Medical College Hospital. They all had history inquiry, physical examination, blood test, cognitive assessment, brain MRI, CSF testing of Aβ42, 181p-tau, and t-tau, and next-generation DNA sequencing. Sixty-nine common single nucleotide polymorphisms (SNPs) (minor allele frequency > 0.01) within or near the coding region of 13 AD susceptible genes were included in the analysis. Results: The rs7412-CC (APOE) genotype showed lower CSF Aβ42 level and higher p-tau/Aβ42 ratio than the rs7412-CT genotype. The rs3752246-C (ABCA7) allele correlated with lower CSF Aβ42 level. The alternate alleles of six ABCA7 SNPs were related to lower CSF p-tau, including rs3745842, rs3764648, rs3764652, rs4147930, rs4147934 and rs881768. The rs11609582-TT (A2M) genotype showed higher CSF p-tau than the rs11609582-TA genotype. The p-tau/Aβ42 ratio was higher in the rs490460-TT (BACE1) genotype relative to the rs490460-GT genotype. Conclusion: Some common variants within or near the coding regions of APOE, ABCA7, A2M, and BACE1 are associated with CSF Aβ42, p-tau. or p-tau/Aβ42.

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Influence of APOE Genotype on Alzheimer’s Disease CSF Biomarkers in a Spanish Population

BioMed Research International ◽

10.1155/2016/1390620 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

J. A. Monge-Argilés ◽

R. Gasparini-Berenguer ◽

M. Gutierrez-Agulló ◽

C. Muñoz-Ruiz ◽

J. Sánchez-Payá ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Apoe Genotype ◽

Amnestic Mild Cognitive Impairment ◽

Spanish Population ◽

Csf Biomarkers ◽

Csf Levels

Objectives. To evaluate the association between apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) levels of Alzheimer’s disease (AD) biomarkers and to study the influence of APOE genotype on the development of AD in a Spanish population.Material and Methods. The study comprised 29 amnestic mild cognitive impairment (MCI) patients and 27 control subjects. Using ELISA methodology, CSF biomarkers and tau/Aβratios were obtained. ANOVA and adjusted odds ratios were calculated.Results. We observed the effect of APOE genotype and age on CSF AD variables. The progression to AD was more clearly influenced by CSF AD variables than by age or APOE status.Conclusions. APOE status influences CSF AD variables. However, the presence of APOEε4 does not appear to be a deterministic factor for the development of AD, because CSF variables have a greater influence on progression to the disease. These results confirm previous observations and, to our knowledge, are the first published in a Spanish population.

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APOE ɛ4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-200556 ◽

2020 ◽

Vol 78 (2) ◽

pp. 587-601

Author(s):

Remy Cardoso ◽

Carolina Lemos ◽

Bárbara Oliveiros ◽

Maria Rosário Almeida ◽

Inês Baldeiras ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Apoe Genotype ◽

Csf Biomarkers ◽

Cognitively Normal ◽

Conversion Time ◽

E4 Allele ◽

Normal Controls

Background: Mild cognitive impairment (MCI) has been considered as a pre-dementia stage, although the factors leading to Alzheimer’s disease (AD) conversion remain controversial. Objective: Evaluate whether TOMM40 poly-T (TOMM40′ 523) polymorphism is associated with the risk and conversion time from MCI to AD and secondly with AD cerebrospinal fluid (CSF) biomarkers, disentangling the APOE genotype. Methods: 147 AD patients, 102 MCI patients, and 105 cognitively normal controls were genotyped for poly-T polymorphism. MCI patients were subdivided into two groups, the group of patients that converted to AD (MCI-AD) and the group of those that remained stable (MCI-S). Results: TOMM40′ 523 L allele was significantly more frequent in the MCI-AD group and having at least one L allele significantly increased the risk of conversion from MCI to AD (OR = 8.346, p < 0.001, 95% CI: 2.830 to 24.617). However, when adjusted for the presence of APOE ɛ4 allele, both the L allele and ɛ4 allele lost significance in the model (p > 0.05). We then analyzed the APOE ɛ4-TOMM40′ 523 L haplotype and observed that patients carrying this haplotype had significantly higher risk (OR = 5.83; 95% CI = 2.30–14.83) and mean lower times of conversion to AD (p = 0.003). This haplotype was also significantly associated with a biomarker profile compatible with AD (p = 0.007). Conclusion: This study shows that the APOE ɛ4-TOMM40′ 523 L haplotype is associated with a higher risk and shorter times of conversion from MCI to AD, possibly driven by CSF biomarkers and mitochondrial dysfunction.

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The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2007.08.019 ◽

2009 ◽

Vol 30 (5) ◽

pp. 672-681 ◽

Cited By ~ 50

Author(s):

Lidia Glodzik-Sobanska ◽

Elizabeth Pirraglia ◽

Miroslaw Brys ◽

Susan de Santi ◽

Lisa Mosconi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apoe Genotype ◽

Normal Aging ◽

Csf Biomarkers

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Joint Effect of ABCA7 rs4147929 and Body Mass Index on Progression from Mild Cognitive Impairment to Alzheimer’s Disease: The Shanghai Aging Study

Current Alzheimer Research ◽

10.2174/1567205017666200317095608 ◽

2020 ◽

Vol 17 (2) ◽

pp. 185-195

Author(s):

Jianxiong Xi ◽

Ding Ding ◽

Qianhua Zhao ◽

Xiaoniu Liang ◽

Li Zheng ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Body Mass Index ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Body Mass ◽

Joint Effect ◽

Genome Wide Association Studies ◽

Risk Genotype ◽

Aging Study

Background: Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies. Methods: We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese community cohort. Conclusion: Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316 participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the log-rank test and Cox regression model. Results: Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio [HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs. non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7 rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However, a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight BMI and AG/AA of ABCA7 rs4147929). Conclusion: ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their risk for incident AD.

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Alzheimer's Disease and the Routine Clinical Use of CSF Biomarkers

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527316666170124164854 ◽

2017 ◽

Vol 16 (4) ◽

Cited By ~ 1

Author(s):

Alessandro Martorana

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Csf Biomarkers ◽

Clinical Use

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Race-Related Association between APOE Genotype and Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Journal of Alzheimer s Disease ◽

10.3233/jad-210549 ◽

2021 ◽

pp. 1-10

Author(s):

Wei Qin ◽

Wenwen Li ◽

Qi Wang ◽

Min Gong ◽

Tingting Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Black People ◽

Late Onset ◽

Meta Analysis ◽

Group Analysis ◽

Apoe Genotype ◽

Cochrane Library ◽

Data Sets ◽

Apoe Genotypes

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.

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Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-200759 ◽

2021 ◽

pp. 1-13

Author(s):

Jonathan D. Drake ◽

Alison B. Chambers ◽

Brian R. Ott ◽

Lori A. Daiello ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Functional Impairment ◽

Amyloid Β ◽

Intercellular Adhesion Molecule ◽

Csf Biomarkers ◽

Linear Regression Models ◽

Cognitively Normal

Background: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer’s disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood. Objective: We utilized Alzheimer’s Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD. Methods: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis). Results: Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-β (Aβ 42), total tau, phosphorylated tau (P-tau), or P-tau/Aβ 42 (all < p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent. Conclusion: Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.

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