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Role of the proliferation-related molecules in the pathogenesis of Alzheimer’s Disease

Yates, Sharon Christine (2012)
M.Phil. thesis, University of Birmingham.

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Abstract

The cell cycle theory of Alzheimer’s Disease (AD) states that neurodegeneration is secondary to aberrant cell cycle activity in neurons. Previous studies suggest that this may be partly attributed to alterations in the mTOR pathway, which promotes cell growth and division, and partly to genetic variants on genes responsible for cell cycle control.

In this study we perform a systematic analysis of the rapamycin-regulated genes that are differentially regulated in brain affected by AD compared to control. These genes may serve as novel therapeutic targets or biomarkers of AD. Secondly, we investigate the association of a cancer-associated variant of p21\(^{cip1}\), and a variant of p57\(^{kip2}\), with AD. These cyclin dependent kinase inhibitors are crucial cell cycle regulatory components that function downstream of mTOR. We confirm the association of the p21\(^{cip1}\) SNPs with AD, and inform on the mechanisms by which they cause loss of function. We also show a weak association between variant p57\(^{kip2}\) and AD. Furthermore, we demonstrate that p57\(^{kip2}\) is differentially imprinted in the frontal and occipital lobe; and suggest that AD may be associated with change in the imprinting status of p57\(^{kip2}\) in the brain.

Type of Work:M.Phil. thesis.
Supervisor(s):Bicknell, Roy and Nagy, Zsuzsanna
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:QH301 Biology
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Institution:University of Birmingham
ID Code:3648
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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