Polymorphism of ApoE in Alzheimer's Disease: Genetic Study in Castile and Leon (Spain)

Alzheimer Disease Clinical Trial

Official title:

Alzheimer's Disease as a Sociosanitary Priority: ApoE Gene Polymorphism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06275243
• Other study ID #: ETICA-ULE-021-2022
• Status: Completed
• Phase: N/A
• Start date: July 6, 2022
• Est. completion date: March 22, 2024

Study information

• Verified date: May 2024
• Source: Universidad de León
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The general objective of this randomized and longitudinal clinical study was to estimate the frequencies of ApoE variants both in the user population of the "Messengers of Peace" Residences and the "Associations of Relatives of Alzheimer's Patients" in Castile y Leon, since, due to its geographical location at the crossroads, it has received multiple genetic contributions from both northern Europe, the Mediterranean area and northern Africa.

The main questions it aims to answer are:

• What are the allelic frequencies of ApoE variants in the population of individuals with Alzheimer's disease in Castile and Leon?

• Is there a correlation between the ApoE4 variant and the lipid profile in the blood of individuals with Alzheimer's disease in this region?

Description:

In the context of Alzheimer disease research, it is widely recognized that the ApoE gene plays a fundamental role in the genetic predisposition of this disease. With three major alleles: ApoE2, ApoE3, and ApoE4, genetic variability in the ApoE gene has been the subject of extensive attention in previous research and its association with increased risk of Alzheimer's disease has remained consistent. Within this framework, three hypotheses are proposed focused on understanding the specific influence of ApoE on Alzheimer's disease and exploring the possible underlying mechanisms.

Within this framework, three hypotheses are proposed focused on understanding the specific influence of ApoE on Alzheimer disease and exploring the possible underlying mechanisms:

1. - Research hypotheses: The genetic variant ApoE4/4 is significantly related to a higher risk of developing Alzheimer's disease compared to individuals who do not carry this genotype.

2. - Research hypotheses: The ApoE2/2 genetic variant is associated with a lower risk of developing Alzheimer's disease compared to other genotypes.

3. - Research hypotheses: People who carry the ApoE4 isoform have elevated levels of total cholesterol and LDL-cholesterol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 511
• Est. completion date: March 22, 2024
• Est. primary completion date: March 13, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 90 Years

Eligibility

Inclusion Criteria:

• Be between 60 and 90 years old.

• Subjects with a diagnosis of AD in the case group.

• Subjects free of AD diagnosis in the control group.

• Subjects who voluntarily and consented to participate free of charge.

• Have completed the written consent

Exclusion Criteria:

• Subjects who, at the time of sample collection, had behavioral or other alterations that made the sample collection procedure impossible.

• Subjects who, at the time of sample collection, presented oral alterations incompatible with the technique.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Diagnostic Test:
• Kit Buccal swab collection & stabilization de Canvax®
Assessment of ApoE variant in saliva samples as a potential biomarker for Alzheimer's disease.

Other:
• Cholesterol levels according to ApoE Genotype
Enhancing the quality of life of study participants by investigating cholesterol levels based on their ApoE genotype.
• Assessing cardiovascular risk factors in all participants
Through individual interviews, record cardiovascular factors and assess their correlation with Alzheimer's disease.

Locations

Country	Name	City	State
Spain	University of León	León

Sponsors (2)

Lead Sponsor	Collaborator
Universidad de León	Consejo General de Colegios Oficiales de Enfermería España

Country where clinical trial is conducted

Spain, 

References & Publications (7)

Alharbi KK, Syed R, Alharbi FK, Khan IA. Association of Apolipoprotein E Polymorphism with Impact on Overweight University Pupils. Genet Test Mol Biomarkers. 2017 Jan;21(1):53-57. doi: 10.1089/gtmb.2016.0190. — View Citation

Eisenberg DT, Kuzawa CW, Hayes MG. Worldwide allele frequencies of the human apolipoprotein E gene: climate, local adaptations, and evolutionary history. Am J Phys Anthropol. 2010 Sep;143(1):100-11. doi: 10.1002/ajpa.21298. — View Citation

Gonzalez RD, Gomes I, Gomes C, Rocha R, Duraes L, Sousa P, Figueruelo M, Rodriguez M, Pita C, Hornero R, Gomez C, Lopes AM, Pinto N, Martins S. APOE Variants in an Iberian Alzheimer Cohort Detected through an Optimized Sanger Sequencing Protocol. Genes (Basel). 2020 Dec 22;12(1):4. doi: 10.3390/genes12010004. — View Citation

Pantelidis P, Lambert-Hammill M, Wierzbicki AS. Simple sequence-specific-primer-PCR method to identify the three main apolipoprotein E haplotypes. Clin Chem. 2003 Nov;49(11):1945-8. doi: 10.1373/clinchem.2003.021683. No abstract available. — View Citation

Reales G, Hernandez CL, Dugoujon JM, Novelletto A, Cuesta P, Fortes-Lima C, Rodriguez JN, Calderon R. New insights into the distribution of APOE polymorphism in the Iberian Peninsula. The case of Andalusia (Spain). Ann Hum Biol. 2014 Sep-Oct;41(5):443-52. doi: 10.3109/03014460.2013.877966. Epub 2014 Feb 6. — View Citation

Reitz C, Mayeux R. Use of genetic variation as biomarkers for Alzheimer's disease. Ann N Y Acad Sci. 2009 Oct;1180:75-96. doi: 10.1111/j.1749-6632.2009.04945.x. — View Citation

Salameh TS, Rhea EM, Banks WA, Hanson AJ. Insulin resistance, dyslipidemia, and apolipoprotein E interactions as mechanisms in cognitive impairment and Alzheimer's disease. Exp Biol Med (Maywood). 2016 Sep;241(15):1676-83. doi: 10.1177/1535370216660770. Epub 2016 Jul 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Distribution of ApoE variants in the Alzheimer's disease population diagnosed in Castile and Leon.	The saliva samples will be processed to purify and extract DNA. Subsequently, a PCR amplification will be performed to check the ApoE alleles and genotypes.	9 months
Secondary	Cardiovascular factors in individuals with Alzheimer's disease and healthy subjects.	We will analyze whether there are significant differences between individuals with Alzheimer's disease and healthy subjects in terms of cardiovascular risk factors (Diabetes mellitus, cardiac pathology, hypercholesterolemia and high blood pressure) using the z-test for difference in proportions.	9 months
Secondary	ApoE genotypes and cholesterol levels in the Alzheimer's disease population diagnosed in Castile and Leon.	To assess the presence of significant differences in the mean cholesterol values across different genotypes, an analysis of variance (ANOVA) test will be applied.	9 months