It has been suggested that infection with Chlamydia may play a role in the initiation/progression of Alzheimer’s disease (AD). To evaluate this hypothesis APP/PS transgenic mice (genetically manipulated to express AD pathology) and wild type (Wt) mice were infected with C. muridarum, and magnetic resonance imaging (MRI) and histopathology were used to assess pathological changes. Congo red staining of tissue sections demonstrated no AD plaque pathology in Wt infected and non-infected mice, while clear pathology (neuritic plaques) was seen in transgenic mice, with a trend towards higher plaque counts in the brains in the infected transgenic mice. When MRI was used to evaluate the effects of infection in vivo, hyperintensities in T2 times were observed in APP/PS infected mice compared to APP/PS control mice both at month 5 and month 20. Together these results suggest that infection with Chlamydia may accelerate the development of AD.

Research on the etiological characteristics of Alzheimer's disease has yielded inconsistent results. It is suggested that this may be due to the unidirectional focus on biomedical attributes, and the failure to consider psychosocial factors in combination with the biomedical characteristics. A biopsychosocial model of Alzheimer's disease, which integrates the biomedical dimension with psychosocial stressors and social support is proposed and tested in a sample of 172 geriatric patients using polychotomous logistic regression. Results find support for the implication of stress in the disease process, but fail to find a relationship between social support and Alzheimer's disease. It is concluded that the ultimate value of a biopsychosocial model of Alzheimer's disease rests in its identification of psychosocial factors, that could result in the prevention of the development of the disease.

Thesis (M A(Psychology))--University of Pretoria, 2008. / Includes bibliographical references. Available on the Internet via the World Wide Web.

Thesis (M. Med. Sc.)--University of Hong Kong, 2008. / Includes bibliographical references (p. 63-96)

Thesis (M.A.)--Eastern Illinois University, 1998. / Includes bibliographical references (leaves 42-45).

Thesis (Ph. D.)--Ohio State University, 2004. / Document formatted into pages; contains 241 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2005 July 27.

Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 248-272). Available also in a digital version from Dissertation Abstracts.

Alzheimer’s disease is the most common cause of late-life dementia and the fourth leading cause of death in the developed world. The aetiology of AD has not yet been resolved. It has been suggested that AD could result from multifactorial process involving both a genetic predisposition and an exposure to environmental factors modulated by the biological aging process. To date, epidemiological and molecular genetic data have led to the identification of three genes, amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) genes, which, when mutated, can cause an early onset form of AD. Genetic linkage studies and association studies have also shown that the ε4 allele of the apolipoprotein E gene increases risk for AD in a dose dependent manner in both early onset and late onset AD. Recently, it has also been suggested that environmental factors may interact with a genetic predisposition to modify the risk of AD. Extensive research is underway to identify environmental and genetic risk factors for this complex disease. Over 40 genes have been tested as AD candidates yet none has been clearly established as an AD risk factor. Currently scientists are investigating the interrelationship between various gene loci and how environmental factors could affect an individual’s susceptibility to AD. This study evaluated the genotoxicity of environmental agents such as hydrogen peroxide, cadmium chloride and γ radiation induced oxidative DNA damage in lymphocytes and within specific DNA sequences of APP (exon 15-18) and PS1 (exon 3-12) genes of AD patients and age-matched control subjects. As indicators of oxidative DNA damage, the frequencies of DNA strand breaks, oxidized pyrimidines and altered purines was assessed using the alkaline Comet assay modified with lesion-specific endonucleases, endo-III and fpg; and fluorescence in situ hybridisation. The number of APP and PS1 hybridisation spots per comet were used as an indicator of the extent of damage. The location of the hybridisation spots in the head or tail of the comet were recorded to further determine whether the gene of interest lies within or in the vicinity of a damaged region of DNA. With the alkaline Comet assay modified with endo-III and fpg, it was demonstrated that patients with AD had significantly increased levels of DNA strand breaks, oxidized pyrimidines and altered purines induced by hydrogen peroxide, cadmium chloride and γ radiation compared with control subjects (p<0.05). This was further confirmed by the fluorescence in situ hybridisation modification of the alkaline Comet assay by demonstrating a significant increase in the mean number of APP and PS1 gene hybridisation spots per comet in AD patients compared with control subjects. Moreover, the gene sensitivity index of APP and PS1 to hydrogen peroxide, cadmium chloride and γ radiation were found to be higher in AD patients than in control subjects. Taken together, our results suggest (i) that lymphocytes from patients with AD are sensitive to these environmental genotoxic agents and (ii) there was an overall increase in the mean number and sensitivity index of APP and PS1 genes to environmental genotoxic agents which might link a genetic cause to oxidative stress in peripheral cells of AD patients than in control subjects. Although the mechanisms by which these environmental agents induced oxidative DNA damage remained to be elucidated, our data suggest that increased oxidative stress is an inherent property of cells carrying genes associated with AD. / Dr. H. Abrahamse Mrs. J. V. Hind

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