Abstract not available

M.A. (Psychology) / Please refer to full text to view abstract

D.Litt. et Phil. (Psychology) / The aim of this study was to investigate the effect that hypertension has on brain function. A neuropsychological test battery comprising of the following tests was employed as a multivariate measure of brain dysfunction in a quasiexperimental, matched group design: a) The Complex Figure Test of Rey (copy, immediate recall and delayed recall), b) the Logical Memory Test, c) the Digits Span Test, d) the Verbal Paired Associate Learning Subtest, e) the Controlled Oral Word Generation Test, fr the Trail Making Test, and the Digit Symbol Substitution Subtest, This permitted a comparison in brain functioning between a group of hypertensive and a group of normotensive participants that were matched according to age, handedness, level of education and sex. The matching of variables increased the sensitivity of the study by controlling extraneous variables and ensured that the groups were compatible on the paired variables. The results were statistically analyzed by employing the Mann-Whitney U statistic for small groups and the Chi-square statistic on the measured variables. Further, content analysis was employed to test for significant differences in strategies of coping, immediate recall and delayed recall of the Complex Figure of Rey. The results indicated that: 1. there were significant differences in attention and concentration, motor functioning, perceptual abilities, information processing, memory, and planning and organisation between the two groups, with the hypertensive group obtaininq significantly lower scores on test measuring these variables; and 2. there were no significant differences in the verbal abilities (word fluency) of the two groups. The results support previous research, finding indications of vocal lesions located across the brains of people suffering from hypertension. Practical implications of the results are discussed and recommendations for future research have been made...

T cells infiltrate the degenerating brain and influence central nervous system (CNS) inflammation and neuronal health. In mice, the choroid plexus and the meninges have been implicated in regulating T cell entry and egress from the CNS, respectively. Further, antigen presenting cells in the mouse meninges present CNS-derived antigens to T cells and may represent a method for the peripheral immune system to sense and respond to CNS immune triggers. However, whether these processes occur in the human choroid plexus and meninges has not been comprehensively studied. Further, the antigens towards which T cells in the degenerating human brain and its borders respond remain unknown. Therefore, I implemented a multi-omics approach using fresh postmortem tissue from patients diagnosed with amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s disease (PD), and non-neurodegenerative controls to identify not only the T cell-associated changes that occur in the degenerating human CNS and surrounding tissues but also identified a library of putative antigen targets for disease-associated T cell populations. Specifically, using single cell RNA and TCR sequencing information from paired postmortem choroid plexus, leptomeninges, and brain I lineage traced T cells using their TCR information and found that T cell access to leptomeninges and brain is likely limited and controlled by anti-inflammatory macrophage activity at the blood/CSF barrier (BCSFB). Once past the BCSFB, I present evidence that T cells access the CNS where they interact with MHC expressed by microglia. T cells also accumulate in the leptomeninges where they become tissue resident memory T cells. These tissue resident memory T cells likely serve as a reservoir for a rapid antigen-driven immune response to future CNS inflammatory insults. Finally, by performing immunopeptidomics to identify peptides presented by MHC in the same patients’ CNS and border tissues, I identified a library of putative antigenic triggers that may drive high levels of T cell clonal expansion in the brain and surrounding tissues. Altogether, this thesis serves as a resource for understanding the trajectory of T cells as they travel into the degenerating human brain and as a foundation for the development of antigen-specific precision medicines to treat neurodegeneration.