The Effect of Chronic Hypertension on Neuropathology in the TGSWDI Mouse Model of Alzheimer's Disease

<p>Numerous epidemiological studies link vascular disorders, such as hypertension, diabetes and stroke, with Alzheimer's disease. Hypertension, specifically, is an important modifiable risk factor for late onset Alzheimer's disease. Despite the abundance of clinical data connecting these conditions, animal studies investigating the connection between the two are lacking. To examine the link between midlife hypertension and the onset of Alzheimer's disease later in life, chronic hypertension was induced in the TgSwDI mouse model of Alzheimer's disease in early adulthood using long-term administration of the eNOS inhibitor, Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). L-NAME treatment accelerated cognitive deficits, microvascular deposition of the amyloidbeta peptide, vascular inflammation, blood brain barrier leakage, and pericyte loss in these mice. Though lysosomal markers were increased in hypertensive TgSwDI mice relative to all other groups, autophagic structures appeared to be increased in both hypertensive TgSwDI mice, as well as hypertensive WT mice. The increased presence of these structures altered cellular morphology at the neurovascular unit and compromised the blood brain barrier in hypertensive mice. Additionally, midlife hypertension induced hippocampal neurodegeneration at an early age in TgSwDI mice. Neuronal loss is a defining characteristic of pathology in Alzheimer's disease, but is not replicated in many mouse models of the disease. Therefore, this may be a useful research model of Alzheimer's disease with mixed vascular and amyloid pathologies and may display classical features of the disease missing in more canonical mouse models.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year

2015

Author dc:creator

• Kruyer, Anna

Contributors dc:contributor

• Sidney Strickland

• hypertension
• Alzheimer's disease (AD)
• TgSwDI mouse model
• amyloid-beta
• blood-brain barrier
• neurodegeneration
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/281

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1282