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GAP43 AS A POTENTIALBIOMARKER FORNEURODEGENERATION: Division of Affinity Proteomics, SciLifeLabDepartment of Protein Science
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
2018 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by progressivedamage and loss of neurons. Despite the efforts, the scientific community still lacks current insights intothe onset and progression of this disease. Previous multiplex analysis of cerebrospinal fluid (CSF)protein profiles on the suspension bead array (SBA) platform, applied in the context of AD, hasunderlined growth-associated protein’s 43 (GAP43 or neuromodulin) association to the disease. GAP43is a brain enriched cytoplasmic protein involved in neuronal growth and axonal regeneration. Becauseof its post translational modifications, mainly phosphorylation, GAP43 plays an important role in memoryand learning. This project aims to further explore the relation of GAP43 to AD through the identificationof antibodies that can capture this protein and their application on Western blot (WB) and brain tissuemicroarray (TMA) protocols. Our antibody selection includes eight antibodies, two of which target thephosphorylated GAP43 (ph-GAP43). All antibodies were tested on Western blots of CSF pools of ADcases and controls with elevated and decreased GAP43 levels respectively. Additionally, four of theseantibodies were tested on TMAs consisting of cortical tissue cores from ten AD patients, ten patientswith Lewy Body Dementia (DLB) and nine controls. Our results indicate that although all antibodiessuccessfully detected GAP43 both on WB and TMAs, ph-GAP43 was only captured on TMAs.Immunohistochemical analysis of temporal and frontal cortex from AD patients revealed an almostcomplementary pattern of GAP43 and ph-GAP43 higher expression in cortical tissue cores obtainedfrom AD patients compared to controls. Lastly, more intense phosphorylation was observed in temporalthan in frontal cortex.

Abstract [sv]

Alzheimers sjukdom är en vanlig neurodegenerativ sjukdom som karaktäriseras av progressiv skadaoch förlust av neuroner. Trots alla försök så saknar fortfarande det vetenskapliga samhället kunskap omhur sjukdomen inträffar och fortskrider. Tidigare multiplex analyser av proteinprofiler fråncerebrospinalvätska (CSF) på suspension bead array (SBA), applicerade på Alzheimers, har betonatkopplingen mellan growth-associated protein's 43 (GAP43 eller neuromodulin) och sjukdomen. GAP43är ett cytoplasmiskt protein, som återfinns till hög koncentration i hjärnan, som är invoverad i neuronaltillväxt och axonal regeneration. På grund av dess post-translationala modifikationer, främstfosforylering, spelar GAP43 en viktig roll i minnets och lärandets mekanismer. Detta projekt fokuserarpå att vidare utforska relationen mellan GAP43 och Alzheimers sjukdom genom identifiering avantikroppar som kan binda proteinet och deras applicering på Western blot (WB) och brain tissuemicroarrays (TMA). Vårt urval av antikroppar inkluderar åtta antikroppar, två av vilka binder detfosforylerade GAP43 (ph-GAP43). Alla antikroppar testades på Western Blot på poolade CSF-proverfrån AD-patienter och kontroller som antingen hade förhöjda eller sänkta GAP43 nivåer. Fyra utav dessaantikroppar testades även på TMAs bestående utav vävnad från tio Alzheimerspatienter, tio patientermed Lewy body sjukdom (DLB) och nio kontroller. Våra tester indikerar att även om alla antikropparframgångsrikt kunde detektera GAP43 på både WB och TMAs så fungerade ph-GAP43 bara på TMAs.Immunohistokemiska analyser av både temporal och frontal cortex från Alzheimerspatienter avslöjadeett nästan komplementärt mönster av GAP43 och ph-GAP43 i cortex från patienter jämfört medkontroller. Slutligen, en högre grad av fosforylering observerades i temporal- än i frontalcortex

Place, publisher, year, edition, pages
2018.
Keywords [en]
GAP43 / Neuromodulin / Alzheimer’s Disease / Suspension Bead Array/ Cerebrospinal fluid
National Category
Other Engineering and Technologies not elsewhere specified
Identifiers
URN: urn:nbn:se:kth:diva-231415OAI: oai:DiVA.org:kth-231415DiVA, id: diva2:1228129
Available from: 2018-06-27 Created: 2018-06-27 Last updated: 2018-06-27Bibliographically approved

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