The blood-brain barrier (BBB) has been recently identified as a key factor involved in the origin and pathological progression of Alzheimer’s disease (AD). The BBB normally plays a role in carefully maintaining the homeostasis of the neural environment by establishing a highly selectively permeable barrier between the CNS and the peripheral microvasculature. Dysfunction of the BBB, also called BBB breakdown, results in altered, usually increased permeability and is a potential early biomarker of AD and cognitive dysfunction. BBB breakdown is either initiated or accelerated by the ε4 variant of the apolipoprotein E (APOE) gene, also known as ApoE4. ApoE4 may impact the BBB through multiple processes including degradation of pericytes, aberrant transport of clotting factors and the key AD biomarker amyloid-β, and disruption of BBB transport mechanisms. This thesis further investigates the degeneration of the BBB in relation to AD using an Evans Blue (EB) dye assay in ApoE4 mice compared with ApoE3 and wild-type (WT) controls. Fluorescent EB dye binds to the macromolecule albumin, which is too large to cross through the highly selective BBB. However, BBB breakdown decreases this selectivity and increases permeability, allowing EB to enter the brain. Intensity of EB dye within brain slices was taken as a measure of BBB permeability. This thesis analyzes the pattern of staining within ApoE4, ApoE3, and WT brains and statistically analyzes the intensity of EB staining across genotype, brain region, and sex groups. We observed concentrated staining in the cortex and hippocampus, as well as the substantia nigra pars reticulata. We found that ApoE4 mice brains contain significantly more BBB disruption than ApoE3 and WT brains. Our findings provide additional insights into the pattern of AD pathology within the brain and confirm that ApoE4 contributes to the degradation of the BBB.
Namkung, Joseph S.,
"Imaging the Breakdown of the Blood-Brain Barrier in Mice with Modeled Alzheimer’s Disease"
(2023).
Neuroscience Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.26300/6x9n-6r25
