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Untersuchungen über die Auswirkungen von Geschlecht und genetischem Hintergrund auf die Alzheimerpathologie im 5xFAD-Mausmodell

dc.contributor.advisorBayer, Thomas A. Prof. Dr.
dc.contributor.authorNordmeyer, Philipp Johannes
dc.titleUntersuchungen über die Auswirkungen von Geschlecht und genetischem Hintergrund auf die Alzheimerpathologie im 5xFAD-Mausmodellde
dc.title.translatedInvestigation of the impact of gender and genetic background on the histopathology in the 5xFAD-mousemodel of Alzheimer's diseasede
dc.contributor.refereeSchulz-schaeffer, Walter J. PD Dr.
dc.description.abstractengAlzheimer's disease (AD) is the most prevalent cause of dementia in the industrial nations. It leads to a constant decline of cognitive capabilities to the point of entire need of care. Since every fifth person over 90 years of age is already affected and prevalence numbers are rising due to the constant aging of population, AD will represent a huge challenge for health systems and economy. Risk factors for developing AD are being found amongst others in genetic mutations which can cause familial AD with early onset. Female gender is also known to have a higher risk of developing AD. Research was able to find a promoting effect of oestrogen on the histopathological hallmarks - accumulation of Beta-Amyloid, neurofibrillary tangles and loss of neurons. In this study the 5xFAD-mousemodel, containing five mutations of familial AD leading to accelerated Beta-Amyloid accumulation, loss of neurons and cognitive decline, is used to investigate the impact of gender and genetic background on the neuronal loss and Beta-Amyloid burden. Design-based stereology for neuron counting and software based proportional determination of immunohistochemically stained areas of Beta-Amyloid were performed in CA1-hippocampus and thalamus after fabrication of brain dissections of 5xFAD-mice of 6 months age with B6/SJL- and pure B6-background. The results showed a significant elevation of Beta-Amyloid burden of female mice confirming that female gender might be affected stronger by histopathological findings in AD. However a significant difference in neuron counting could not be found between genders implicating that a gender driven effect on neuron loss might rise later in progress of AD in 5xFAD. Concerning the genetic background a significant difference in the volume of CA1-hippocampus with lower volumes for B6/SJL could be found supporting findings that genetic background has an effect on neurodegenerative processes. The 5xFAD-mousemodel confirms its usefulness for examining the histopathological hallmarks of AD. Further studies involving this model should be performed investigating the role of gender in familial AD to discover ways for prevention and treatment of
dc.contributor.coRefereeSchön, Margarete Prof. Dr.
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullPsychiatrie (PPN619876344)de

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