Alzheimer‘s disease (AD), which results in disability, is one of the most prevalent neurological conditions in the elderly. The symptoms of disability are includes deterioration in memory, thinking, behavioural and the ability to perform everyday activities. While there is no cure for the symptoms of AD, pharmacological management and non-pharmacological support may help to improve cognitive and behavioural symptoms. Brain derived neutrophic factor (BDNF), which is a protein and a member of the neurotrophin family of growth factors, supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. There is evidence that patients with AD have decreased BDNF concentrations; however, serotonin selective reuptake inhibitors (SSRIs) elevate BDNF. Additionally, there are known BDNF gene Val66Met polymorphism (rs6265/G196A) responsible for BDNF synthesis that impact BDNF function. During the first phase of the research, 123 healthy young, middle ages (25-59 years old) and elderly (more than 60 years old) participants were selected from the King Salman Social Centre (KSSC), to determine whether there were differences in their serum BDNF with a commercially available enzyme-linked Immunosorbent assay (ELISA) kit. The evidence suggested that healthy participants experienced a decrease in serum BDNF concentrations as their age increased. Also, during this phase, a correlated comparison was conducted that evaluated how BDNF concentrations were affected by different variables such as age, body mass index and diabetes mellitus. Throughout the second phase of the study, the patients were recruited from the King Fahad Medical City (KFMC) in Riyadh. The levels of the serum BDNF concentration in AD patients (n=27) was compared to the serum BDNF concentration of healthy elderly participants (n=48). Then, the correlation between the changes in concentrations and cognition functions with assessments tools (Clinical Rating Scales and Mini Mental examination tests) was studied. During the third phase of the study, the impact of SSRIs on serum BDNF concentration and cognition function for both AD patients (n=13) and healthy elderly participants (n=17) were assessed.. The results of this study indicated that the use of SSRIs stimulated BDNF concentrations for both groups (p=0.001), positively improved cognitive function in elderly participants (p>0.001) and did not improve cognitive function in AD patients (p=0.1). The final phase of the study investigated whether the BDNF gene Val66Met polymorphism (rs6265/G196A) in both AD and elderly is associated with cognitions functions changes. The genotyping for the association study was performed in 40 patients and 140 controls of Saudi origin by real-time PCR using Taqman chemistry in the ABI Prism 7900HT Sequence Detection System. The findings demonstrated that the BDNF Val66Met genotype distributions and allele frequencies showed significant association with cognition performance for both the elderly control group and AD patient‘s .The main findings showed that GG homozygotes (Val/Val) have superior cognition performance among AD patients and elderly control groups.
|Date of Award||Nov 2018|
|Supervisor||Paul Gard (Supervisor), Greg Scutt (Supervisor) & Norah Abanmy (Supervisor)|