This week we profile a recent publication in Alzheimer’s & Dementia from the laboratory
of Dr. Tsuneya Ikezu (pictured) at the Boston University School of Medicine.
Can you provide a brief overview of your lab’s research focus?
As Alzheimer’s disease (AD) progresses, misfolded amyloid-β peptide (Aβ) and microtubule-associated protein tau spread in a spatiotemporal manner in the brain. The pathobiology of how tau accumulation spreads to distinct brain regions is poorly understood. My laboratory is focused on how extracellular vesicles (EV) and glia, especially microglia, may contribute to the disease spread. EV biology is relatively new in the neuroscience field. We are, therefore, interested in understanding the function, molecular composition and cellular origin in EVs from human biospecimens, including brain tissue, cerebrospinal fluid, plasma and induced pluripotent stem cell-derived neuronal cells, along with mouse models of AD.
What is the significance of the findings in this publication?
This publication is the first comprehensive quantitative proteomics study of EVs isolated from human AD and control brain tissues. The EVs separated from human AD brain tissue were enriched with pathogenic proteins, such as Aβ, tau, APOE and α-synuclein. Using a machine learning technique, we have identified ANXA5, VGF, GPM6A and ACTZ, which can distinguish AD and control brain-derived EVs with high accuracy. Moreover, a validation cohort study showed that the ANXA5 level was significantly elevated in AD brain-derived EVs. This study demonstrates that EV-associated Aβ and tau, ANXA5, VGF, GPM6A and ACTZ can be utilized as potential biomarkers for monitoring the progression of AD.
What are the next steps for this research?
We plan to follow up the study by examining the specificity to AD by comparing EVs isolated from other tauopathy, such as chronic traumatic encephalopathy, progressive supranuclear palsy, corticobasal degeneration, and by evaluation of the pathogenic roles of these molecules on the spread and propagation of tau in cells and animal models. We also plan to examine if these candidate molecules are also useful AD biomarkers in EVs separated from patient plasma and cerebrospinal fluid.
This work was funded by:
This work was funded by National Institute of Health, Alzheimer’s Association, BrightFocus Foundation, Cure Alzheimer’s Fund and CurePSP.
