NYMC Faculty Publications
Alpha B-Crystallin Potentiates Alzheimer's Disease a Beta Neurotoxicity by Heteroligomeric Stabilization
Author Type(s)
Faculty
Journal Title
Investigative Ophthalmology & Visual Science
First Page
2089
Document Type
Abstract
Publication Date
6-2021
Department
Pediatrics
Second Department
Cell Biology and Anatomy
Abstract
Purpose : We previously reported Aβ accumulation in lenses from patients Alzheimer’s Disease (AD) (Goldstein et al., 2003) and Down syndrome (Moncaster et al., 2010), a common chromosomal disorder in which age-related Aβ brain pathology is an invariant feature. Aβ co-localized with αB-crystallin in these lenses. Here we investigate the molecular mechanisms underpinning αB-crystallin interactions with Aβ and implications for AD pathogenesis.
Methods : Immunohistofluorescence, Confocal Microscopy, Immunogold electron microscopy, SDS-page and immunoblotting, electron paramagnetic resonance spectroscopy (EPR), quasi-elastic light scattering (QLS) spectroscopy, cell and organotypic slice culture, LDH and Propidium iodide assays.
Results : Electron paramagnetic resonance spectroscopy revealed that αB-crystallin dynamically interacts with and binds to Aβ in vitro in concordance with previous findings. Quasi-elastic light scattering spectroscopy showed that αB-crystallin suppresses formation of high molecular weight Aβ aggregates by stabilizing soluble hetero-oligomeric complexes. However, whilst co-incubation of αB-crystallin and Aβ suppressed Aβ fibrillogenesis, αB-crystallin potentiated Aβ neurotoxicity in mouse primary neurons and organotypic rat hippocampus slice culture as detected by LDH and Propidium Iodide assays.
Conclusions : These results indicate that αB-crystallin potentiates Aβ neurotoxicity by stabilizing soluble hetero-oligomers.
This is a 2021 ARVO Annual Meeting abstract.
Recommended Citation
Moncaster, J. A., Sarangi, S., Minaeva, O., Zhang, X., Altman, R. L., Gangalum, R., Sullivan, J., Chen, C., Huber, B., Zeldich, E., Abraham, C., Bhat, S. P., Voss, J., Hartley, D., Stanton, P. K., & Goldstein, L. E. (2021). Alpha B-Crystallin Potentiates Alzheimer's Disease a Beta Neurotoxicity by Heteroligomeric Stabilization. Investigative Ophthalmology & Visual Science, 62 (8), 2089. Retrieved from https://touroscholar.touro.edu/nymc_fac_pubs/4800