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Exploring the neuropathological impact of ace1 gene in alzheimer's disease

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  1. Tez No: 912518
  2. Yazar: ÖZGE GÜZEL
  3. Danışmanlar: PROF. DR. PATRİCK KEHOE, DR. SCOTT MİNERS
  4. Tez Türü: Yüksek Lisans
  5. Konular: Genetik, Genetics
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2019
  8. Dil: İngilizce
  9. Üniversite: Unıversıty Of Brıstol
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Sağlık Bilimleri Ana Bilim Dalı
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: Belirtilmemiş.

Özet

Background: Angiotensin converting enzyme-1 (ACE1) is a candidate risk gene for Alzheimer's disease (AD). ACE1 plays and crucial role in regulation of blood pressure and clearance of β-amyloid (Aβ). Relevant literature has highlighted that ACE1 variant, an indel polymorphism (rs4343), has been shown to be associated with increased risk of AD. Hypothesis and aim: The aim of the study was to investigate whether the ACE1 variant (rs4343) was associated with the formation of Aβ plaques and tau tangles in pathology of AD. We hypothesised that the AD risk associated genotypes (I/I and I/D) are associated with increased markers of disease pathology in AD. Methods: We studied a total cohort of 169 AD and 104 controls. Parenchymal Aβ plaques and tau tangles load was quantified by computer-assisted field fraction analysis in the frontal, parietal and occipital lobes in 61 cases. The ACE1 indel polymorphism, rs4343, was genotyped in 154 cases. We performed t-test to determine the association between ACE1 genotype and AD. Results: ACE1 genotypes were not significantly associated the risk of AD. Moreover, The ACE1 indel polymorphism was not associated with either Aβ or tau parenchymal load. On the other hand, parenchymal Aβ and tau load in the frontal, parietal and occipital lobes and the risk of AD were strongly associated (p values <0.0001). Conclusion: The ACE1 indel polymorphism did not have impact on amyloid and tau pathology and AD. To develop a full picture of ACE1 genotype in AD, larger cohort study with greater statistical power would be helpful.

Özet (Çeviri)

Alzheimer's disease (AD) is the most common cause of dementia, accounting for two-thirds of cases in elderly. Two pathological abnormalities, amyloid plaques and tau tangles, in the brain. The cause of AD and the factors that contribute to the build up of plaques and tangles is still unknown. Recent studies suggest that genetic risk factors i.e. changes in genes that increase the risk of AD, account for up to 60-70% of risk associated with AD. One candidate gene is ACE1 which is responsible for regulating blood pressure. In the light of these findings, the hypothesis of study was that ACE1 genotype would be associated with elevated level of Aβ and Tau. We first genotyped ACE1 indel polymorphism in 154 cases and then measured Aβ and Tau in 61 cases in post-mortem brain tissue. After that, we combined them with obtained data by other researchers. Totally, we had 169 AD cases and 104 controls in the cohort study. We verified the association between AD-related neuropathological changes and AD but ACE1 genotype significantly associated with neither AD nor Aβ and tau load couldn't find. Our data suggest that there is no relationship between ACE1 genotype and neuropathology. These findings may be somewhat limited by small size of sample. Therefore, we need a larger cohort study be sure of our results.

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