Alzheimer’s disease (AD) is the predominant form of age-related dementia, and presents with multifactorial etiology. The accumulation of amyloid (Aβ) plaques, followed by tau tangles, ultimately contributes to synaptic dysfunction, atrophy, and eventually cognitive decline. The glymphatic system works to clear waste from the brain. Emerging evidence suggests that dysfunctional clearance of Aβ may exacerbate its aggregation and accelerate AD progression, particularly in the preclinical stages of the disease. The exact mechanism is unknown.

Serena Tang is a graduate student in Dr Tosun's lab who has been working on characterizing the role of glymphatic clearance in AD by designing computational tools to quantify perivascular spaces, the structural component of the glymphatic system. She is using statistical methods to unravel their relationship to drivers of glymphatic function and biomarkers of AD, namely cerebrovascular function and sleep. In leveraging large, multi-modal datasets (e.g. the Alzheimer’s Disease Neuroimaging Initiative (ADNI)) and experimental datasets to study these relationships across the AD continuum, her work will provide a better understanding of the brain’s waste clearance system to unravel the early pathophysiology of AD and unveil modifiable factors that can slow AD progression and preserve cognitive health.

Serena presented her work at two conferences in poster format, sharing results from an investigation of relationships between enlarged perivascular spaces (EPVS) as a measure of glymphatic clearance integrity, white matter hyperintensities (WMH) as a measure of cerebrovascular integrity, along with Aβ and APOE ε4 genotype as biomarkers for AD pathology risk. The analysis aimed to understand how cerebrovascular and glymphatic-related deficits may precede and influence AD pathology. The main finding was that EPVS and WMH not only generally increase with disease severity, but also their relationship with each other changes across the disease spectrum. Those diagnosed with mild cognitive impairment (MCI) had a stronger association between EPVS and WMH compared to those who were cognitively unimpaired (CU). This was also true of those who were positive for amyloid burden or carried at least one APOE-ε4 allele despite being considered cognitively unimpaired. In addition, there were differences in the associations between the rates of change of EPVS and WMH. 

Conference presentations: Society for Neuroscience (SfN, 2024) and Alzheimer's Association International Conference (AAIC, 2024)