Study of abeta aggregates as a diagnostic target and TREM2 as a potential therapeutic target in Alzheimer’s disease

Alzheimer’s disease is a neurological disorder and the most common cause of dementia. When considering the pathology of Alzheimer’s disease, Aβ plaques are one of the major pathological hallmarks of Alzheimer’s disease. In the first research project binding of a PET tracer, flutemetamol to Aβ 1-40 was studied using isotopically labeled Aβ 1-40, which was expressed in E. coli. Binding studies were performed using HPLC to determine the binding stoichiometry of flutemetamol with Aβ 1-40 fibrils. Then, solid state NMR was used to determine the binding sites in Aβ 1-40 fibrils. My second project was focused on triggering receptor expressed on myeloid cells 2 (TREM2), a cell surface receptor known to activate the signaling pathway of the phagocytosis of cellular debris, lipoproteins, Aβ amyloid aggregates and bacteria. This makes TREM2 receptor a promising target for therapeutic development to treat AD. We have developed an efficient method for chemically synthesizing the ectodomain of TREM2 using solid-phase peptide synthesis. This methodology was applied to synthesize the TREM2 ectodomain with site-specific modifications such as fluorescence labeling and biotinylation. We believe these TREM2 constructs would allow for a better understanding of TREM2 for the use of future therapeutic strategies such as enhancing microglial activation by targeting this receptor. As my side projects, several proteoforms, histones, CHH (crustacean hyperglycemic hormone) and, VIH (vitellogenesis inhibiting hormone) with post-translational modifications were chemically synthesized with high purity for the separation using mass spectrometric techniques which will be useful in epigenetic and diagnostic studies.

Author

• Wijegunawardena, Gayani Madusha

Identifier

hdl:10057/25414

OAI identifier oai:identifier

oai:soar.wichita.edu:10057/25414