Nicole Phan began working under Dr. Green as a lab assistant and developed a tremendous interest in their research. She discussed the possibility of conducting an independent project within the lab and began this work investigating cerebral amyloid angiopathy. Nicole particularly enjoyed the unpredictability of research, and the excitement of knowing that a final outcome can be completely different than original directions might have suggested. After graduation, Nicole plans to apply to medical school.

Alzheimer’s disease (AD) is an age-related, progressive neurodegenerative disorder characterized by the presence of β-amyloid (Aβ) plaques and neurofibrillary tangles. Over 90% of AD patients with confirmed plaques and tangles also exhibit cerebral amyloid angiopathy (CAA). Microglia are believed to regulate Aβ accumulation and deposition in AD, with failures in immune clearance mechanisms believed to underlie the onset of AD. Our lab has demonstrated that microglia in healthy adult mice depend on colony-stimulating factor 1 receptor (CSF1R) signaling for survival, and inhibition of CSF1R results in rapid global elimination of microglia. We found that administration of the CSF1R inhibitor, PLX5622, in pre-pathological 5xfAD animals results in the appearance of CAA. To extend these findings, we sought to characterize the consequences of CAA induction on the local brain environment. If microglia protect against CAA onset and blood vessel damage to the cortex in 5xfAD animals, then the elimination of microglia should worsen the blood-brain barrier (BBB) integrity and blood vessel-associated tissue necrosis. Cohorts of animals treated for 3 and 6 months underwent immunohistochemical analysis for endothelial components and markers of brain bleeding. The findings indicate that microglia play a protective role against CAA-induced damage, specifically within the thalamus.

Kim Green School of Biological Sciences

Nicole’s work highlights the importance of microglia in protecting the aged brain from the development of cerebral amyloid angiopathy (CAA). CAA is the accumulation of the amyloid-beta peptide in the blood vessels of the brain and is associated with the development of Alzheimer’s disease as well as with increased risk of stroke. Nicole worked independently to assess the consequences of CAA that accumulated due to the pharmacological depletion of these microglia in mouse models of Alzheimer’s disease. She learnt several advanced laboratory techniques, and was able to show that CAA disrupts the integrity of the blood vessels. Projects like this highlight the importance of research-intensive Schools such as UCI, and the high caliber of our undergraduate students, and provide unique training and experiences that will serve Nicole and others well in their future careers.