The role of Amyloid-beta oligomers in the developing CNS

Session Number

Project ID: BIO 33

Advisor(s)

Dr. Samuel Bartley; Northwestern University

Discipline

Biology

Start Date

22-4-2020 10:25 AM

End Date

22-4-2020 10:40 AM

Abstract

The buildup of Amyloid-beta oligomers (AβO) is regarded as a central toxic event in Alzheimer’s disease. 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 eggshell 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 goal is to close the injection-dissection window to determine the “critical window” of gibba formation

Share

COinS
 
Apr 22nd, 10:25 AM Apr 22nd, 10:40 AM

The role of Amyloid-beta oligomers in the developing CNS

The buildup of Amyloid-beta oligomers (AβO) is regarded as a central toxic event in Alzheimer’s disease. 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 eggshell 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 goal is to close the injection-dissection window to determine the “critical window” of gibba formation