The role of Amyloid-beta oligomers in the developing CNS
Advisor(s)
Samuel Bartley; Northwestern University
Discipline
Biology
Start Date
21-4-2021 10:05 AM
End Date
21-4-2021 10:20 AM
Abstract
The buildup of Amyloid-beta oligomers (AβOs) is regarded as a central toxic event in Alzheimer’s disease (AD) development. Recently, AβOs have been found in the developing chick retina but do not cause a disease state. Conserved by evolution, the functional role of these AβOs in retinal development is not currently known. Our team in the Klein Lab has found that these AβOs are transiently expressed, appearing in retinal layers associated with nerve cell death as well as synapse formation. Using an ex-ovo culture method and intravitreal injections, we can manipulate the expression of AβOs in the chick retina to observe developmental changes. Chick embryos are grown outside of the egg shell to E9 and receive an intravitreal injection of either a BACE-1 inhibitor or an AβO antibody. The eyes are then dissected at E15 and stained with antibodies for fluorescence microscopy. Our team has found that inhibiting AβO function between E9-E15 induces significant disruptions in retina lamination, forming omega and polyp-like protrusions dubbed “gibba”. Our current project focuses on the function of NaK-ATPase and its relation to AβOs in two competing outlooks: whether AβOs are inhibiting the enzymatic activity of the NaK-ATPase or are disrupting the localization of NaK-ATPase on cellular membranes.
The role of Amyloid-beta oligomers in the developing CNS
The buildup of Amyloid-beta oligomers (AβOs) is regarded as a central toxic event in Alzheimer’s disease (AD) development. Recently, AβOs have been found in the developing chick retina but do not cause a disease state. Conserved by evolution, the functional role of these AβOs in retinal development is not currently known. Our team in the Klein Lab has found that these AβOs are transiently expressed, appearing in retinal layers associated with nerve cell death as well as synapse formation. Using an ex-ovo culture method and intravitreal injections, we can manipulate the expression of AβOs in the chick retina to observe developmental changes. Chick embryos are grown outside of the egg shell to E9 and receive an intravitreal injection of either a BACE-1 inhibitor or an AβO antibody. The eyes are then dissected at E15 and stained with antibodies for fluorescence microscopy. Our team has found that inhibiting AβO function between E9-E15 induces significant disruptions in retina lamination, forming omega and polyp-like protrusions dubbed “gibba”. Our current project focuses on the function of NaK-ATPase and its relation to AβOs in two competing outlooks: whether AβOs are inhibiting the enzymatic activity of the NaK-ATPase or are disrupting the localization of NaK-ATPase on cellular membranes.