Search for a Profile of Biomarkers for Alzheimer's Disease: Focus on
Genes of the Inflammatory Pathway.

Name: LÍGIA RAMOS DOS SANTOS

Publication date: 20/02/2017
Advisor:

Name	Role
FLAVIA DE PAULA (M/D)	Advisor *

Examining board:

Name	Role
FLAVIA DE PAULA (M/D)	Advisor *
FLAVIA IMBROISI VALLE ERRERA	Internal Examiner *
RENATO LIRIO MORELATO	External Examiner *

Summary: SANTOS, L.R. Search of Biomarker's profile for Alzheimer disease: focus on
genes of inflammatory pathway. 2017. 130 f. Dissertation (Master in
Biotechnology) – Programa de Pós-Graduação em Biotecnologia, Universidade
Federal do Espírito Santo, Vitória, 2017.
Alzheimer disease (AD) is a progressive neurodegenerative disease and the most
common type of dementia that affects elders. As pathological features, it presents
neurofibrillary tangles and amyloid plaques in the brain. In 98% of the cases, AD is
sporadic or late-onset AD (LOAD) and the ɛ4 allele of APOE gene acts as the most
risk factor. As the pathological events may appear years before the first symptoms of
AD, the research seek to use biomarkers in AD pre-clinic phase to identify traces of
the disease before it establishment. Therefore, the work aimed investigate the
creation of a possible genetic biomarkers profile for Late-onset Alzheimer disease
with the polymorphisms at the genes ABCA7 (rs3764650), MS4A6A (rs610932),
CD33 (rs3865444), CR1 (rs6656401), BIN1 (rs744373), IL-6 (rs1800795), CLU
(rs1136000) and APOE (rs429358 and rs7412) in a sample of patients and controls
in Grande Vitória-ES population. The study performed was an association study with
241 individuals not consanguineous, including 159 individuals without Dementia
matched by sex and age and 82 patients with diagnosis of probable AD. It was
performed as genotyping Polymerase Chain Reaction – Restriction Fragment Length
Polymorphism, Real-Time Polymerase Chain Reaction and sequencing of genotype
standards. As statistic analysis, it was performed Chi-square test, Odds ratio,
Confidential interval of 95%, Mann-Whitney and Logistic regression at SPSS
software. It was consider p significance with value < 0.05. It was analyzed statistic
epistasis in pares of polymorphisms from the same pathway to AD by Logistic
regression. It was also calculated the Hardy-Weinberg Equilibrium for each group. It
was found association only for rs3865444 CD33. This polymorphism had showed
association to LOAD with GT genotype as protection factor (95% CI: 0.299-0.942;
p=0.042). This result supports a role of protection of CD33 gene at inflammatory
pathway to LOAD, since the CD33 protein may contribute with A&#946;42 clearence in AD.
The logistic regression analysis did not found association for the others
polymorphisms when associated with others variables as age, gender, school level,
ethnical background and APOE status. In epistasis analysis, it was found risk
association among polymorphisms at APOE with BIN1 and APOE with CLU for
LOAD. Theses results supports a role of APOE, BIN1 and CLU genes at metabolism,
trafficking and endocytosis of lipid pathway in AD. Also, this data support the
hypothesis that APOE and CLU genes may regulate together the elimination of A&#946;
formed in brain. Additionally, the result of interaction of BIN1 and APOE support the
notion that BIN1 protein could participate in A&#946; clearance by the internalization of A&#946;-
apoe complex. The results of the study gave an opening for a creation of a genetic
biomarkers profile for LOAD in Grande Vitória-ES population.
Keywords: Sporadic Alzheimer disease. Biomarkers. Association study.

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