Alzheimer’s disease (AD) has been defined as a type of dementia that causes problems with memory, thinking, and behavior. AD is characterized by tau tangles and Aβ plaques in and around neurons, respectively. The impact this disease has on its victims’ health, both physically and mentally, is unimaginable and the rate of progression is not expected to decrease any time soon. This threat to our minds encourages the importance of understanding AD. Amongst the theories as to what bio mechanisms cause the brain to intertwine is the amyloid cascade hypothesis. The purpose of this thesis is to review the amyloid cascade hypothesis and discuss treatments which utilize this model. We also wish to examine social aspects such as loneliness and socioeconomic factors which are associated with the progression of AD. Research presented provides evidence that targeting the accumulation of Aβ in the brain will prevent further biochemical responses to form neurodegenerative pathology. From the collected data, we observe that therapies targeting the amyloidogenic pathway have received positive feedback in the medical community. Amongst them, an Aβ synthetic peptide vaccine which made history in vaccine development due to their responder rate. The impact of social factors such as loneliness in the advancement of AD is also supported by research. While it is acknowledged that any neurodegenerative disease is far too complex to narrow its cause specifically, this thesis provides an association with multiple aspects that can be understood and applied to future research in this field. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

Thesis (Ph. D.)--University of Chicago, Dept. of Chemistry, June 1999. / Includes bibliographical references. Also available on the Internet

Thesis (Ph. D.)--University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (March 3, 2007) Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 121-158).

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, characterized by global cognitive decline and progressive memory loss. As many other neurological disorders characterized by “proteinopathy”, pathology of AD includes beta-amyloid plaques and tau neurofibrillary tangles, which imply a crucial role of the cellular degradation systems in maintaining homeostasis of protein turnover. This is especially important for post-mitotic neuronal cells since aggravating protein crisis cannot be alleviated by cell division. Autophagy is a cellular degradation process that removes or recycles long-lived proteins and damaged organelles, with its enhancement being remarkably implicated during the progression of Alzheimer’s disease (AD). The majority of studies have hitherto focused on the mechanism of how oligomeric Ah, as one of the potent toxic species in AD, activates autophagy. However, how autophagy is activated remains to be elucidated. The goal of this study is to reveal the underlying mechanisms of autophagy and the subsequent events. Using imaging and biochemical analysis in primary cultures of rat hippocampal neurons, I found that oligomeric An-induced autophagy was initiated by aggregation of the endoplasmic reticulum (ER), in an mTOR-independent pathway. Ao-triggered autophagosomes were derived from omegasomes, starting from the ER aggregation sites. Aggregation of the ER facilitated the clustering of Atg14L to propel the recruitment of Beclin1 and Vps34, which contributes to generation of omegasomes. I further found that p62 targeted to ER aggregates possibly through the enhanced ubiquitinated ER chaperones trapped at ER aggregation sites, implicating the underlying mechanism for how p62 are recruited to autophagosome formation sites (omegasomes). Herein, I report key steps for activation of AH-triggered autophagy, whereby a mechanistic link between ER aggregation, autophagic activation and recruitment of p62 to autophagosome formation sites is revealed. First, Ao-induced ER aggregation triggers autophagy, via the recruitment of Beclin 1 and Vps34 to Atg14L clusters, which is a promoting factor for omegasome formation at the ER aggregation site. Second, the recruitment of p62 to omegasomes is likely mediated by the attraction of the underlying accumulation of ubiquitinated ER chaperones at the ER aggregation site. Up-regulation of autophagy is an early sign of AD. The activation of autophagy without tightly manipulation may contribute to neuronal damage in AD. In addition, how the autophagic substrates can be efficiently incorporated into the autophagic pathway is important for understanding the sustainability of autophagy. Therefore, my study on elucidating how ER aggregation initiates autophagy and the autophagic substrate/cargo receptor p62 are loaded onto autophagosome formation sites may help us to identify a potential therapeutic strategy or target for AD patients. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

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Appendum pasted into front end-papers. / Bibliography: leaves xiii-xliii. / xi, 195, xliii leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Traumatic brain injury (TBI) effects neuronal cell bodies (NCBs), axons and dendrites in a complex fashion, producing a spectrum of damage dependent on the initial injury and secondary effects. Accumulation of amyloid precursor (APP) in NSBs and axons is a feature of TBI. This accumulation may be due to impairment of the axonal transport of APP and/or upregulation of APP mRNA synthesis. This thesis hypothesizes that mechanical deformation, which is not severe enough to cause immediate cell death, results in increased APP mRNA and antigen expression as an acute phase response to injury. / Thesis (Ph.D.)--University of Adelaide, Dept. of Pathology, 1999

Thesis (Ph. D.)--University of Hong Kong, 2007. / Also available online.