The effects of normal aging and ApoE genotype on the levels of 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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Joint Effect of Hypertension and APOE Genotype on CSF Biomarkers for Alzheimer's Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-2010-091198 ◽

2010 ◽

Vol 20 (4) ◽

pp. 1083-1090 ◽

Cited By ~ 14

Author(s):

Maartje I. Kester ◽

Wiesje M. van der Flier ◽

Gorana Mandic ◽

Marinus A. Blankenstein ◽

Philip Scheltens ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apoe Genotype ◽

Joint Effect ◽

Csf Biomarkers

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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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