Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease

JACINTO, JOIC

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Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease / JOIC JACINTO

Swansea University Author: JOIC JACINTO

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Abstract

Since the discovery of the amyloid precursor protein (APP) over 30 years ago, scientists have investigated its involvement in Alzheimer's disease (AD). They have also found speciﬁc cases where mutations in this gene led to the early onset familial form of AD (EOFAD). However, little attention h...

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Published:	Swansea University 2026
Institution:	Swansea University
Degree level:	Master of Research
Degree name:	MSc by Research
URI:	https://cronfa.swan.ac.uk/Record/cronfa71439

first_indexed	2026-02-17T09:33:17Z
last_indexed	2026-02-18T05:35:31Z
id	cronfa71439
recordtype	RisThesis
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spelling	2026-02-17T09:33:15.2872387 v2 71439 2026-02-17 Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease dec7ccf6b378714c2b2a0c60d7e18bd9 JOIC JACINTO JOIC JACINTO true false 2026-02-17 Since the discovery of the amyloid precursor protein (APP) over 30 years ago, scientists have investigated its involvement in Alzheimer's disease (AD). They have also found speciﬁc cases where mutations in this gene led to the early onset familial form of AD (EOFAD). However, little attention has been paid to the structural mechanisms by which these EOFAD mutations trigger AD pathogenesis, probably due to the relatively small percentage of AD patients (<1%) that carry these missense mutations. By using bioinformatics tools (i.e. STRING, Reactome, UCSF Chimera, AlphaFold2, AlphaFold Server) and databases (i.e. ClinVar, UniProt, PDB), APP and the pathological consequences of EOFAD mutations were studied comprehensively. By exploring the network of proteins that APP physically or functionally interacts with, key interactors were identiﬁed. Presenilin-1 (PSEN1) is one of them. PSEN1 is part of the γ-secretase complex, involved in the amyloidogenic processing of APP, leading to the formation of Aβ peptides. Another interactor is the enzyme acetylcholinesterase (ACHE).Their interaction is less known, but they have been found to co-localise in neurons. ACHE is responsible for the hydrolysis and recycling of the neurotransmitter acetylcholine.Investigating the APP-PSEN1 and APP-ACHE complexes at the molecular level provides opportunities for identiﬁcation of key binding amino acids – valuable information for understanding pathological mechanisms and discovering novel drug targets. In the context of EOFAD, some of these APP mutations might be closely involved with such amino acids or might inﬂuence important structural regions involved in their protein-protein interface.These ﬁndings highlight the importance of further investigating the structural intricacies of APP and its interactions, oﬀering new avenues for understanding EOFAD pathogenesis and identifying potential therapeutic targets that could beneﬁt both rare and common forms of AD. E-Thesis Swansea University Bioinformatics, Alzheimer's disease, protein structures, missense variants, APP 30 1 2026 2026-01-30 COLLEGE NANME COLLEGE CODE Swansea University Master of Research MSc by Research del Sol Abascal, R. 2026-02-17T09:33:15.2872387 2026-02-17T09:18:13.2914684 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science JOIC JACINTO 1 71439__36245__2bc0c35dd8154f07bca1fba88d97b7a0.pdf 2024_Majo_Jacinto_J.final.71439.pdf 2026-02-17T09:32:09.5758867 Output 6690621 application/pdf E-Thesis – open access true Copyright: the author, Joic Benjamin Majo Jacinto, 2026. Distributed under the terms of a Creative Commons Attribution Non Commercial 4.0 License (CC BY-NC 4.0) true eng https://creativecommons.org/licenses/by-nc/4.0/
title	Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease
spellingShingle	Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease JOIC JACINTO
title_short	Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease
title_full	Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease
title_fullStr	Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease
title_full_unstemmed	Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease
title_sort	Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease
author_id_str_mv	dec7ccf6b378714c2b2a0c60d7e18bd9
author_id_fullname_str_mv	dec7ccf6b378714c2b2a0c60d7e18bd9_***_JOIC JACINTO
author	JOIC JACINTO
author2	JOIC JACINTO
format	E-Thesis
publishDate	2026
institution	Swansea University
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id	facultyofmedicinehealthandlifesciences
hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id	facultyofmedicinehealthandlifesciences
hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description	Since the discovery of the amyloid precursor protein (APP) over 30 years ago, scientists have investigated its involvement in Alzheimer's disease (AD). They have also found speciﬁc cases where mutations in this gene led to the early onset familial form of AD (EOFAD). However, little attention has been paid to the structural mechanisms by which these EOFAD mutations trigger AD pathogenesis, probably due to the relatively small percentage of AD patients (<1%) that carry these missense mutations. By using bioinformatics tools (i.e. STRING, Reactome, UCSF Chimera, AlphaFold2, AlphaFold Server) and databases (i.e. ClinVar, UniProt, PDB), APP and the pathological consequences of EOFAD mutations were studied comprehensively. By exploring the network of proteins that APP physically or functionally interacts with, key interactors were identiﬁed. Presenilin-1 (PSEN1) is one of them. PSEN1 is part of the γ-secretase complex, involved in the amyloidogenic processing of APP, leading to the formation of Aβ peptides. Another interactor is the enzyme acetylcholinesterase (ACHE).Their interaction is less known, but they have been found to co-localise in neurons. ACHE is responsible for the hydrolysis and recycling of the neurotransmitter acetylcholine.Investigating the APP-PSEN1 and APP-ACHE complexes at the molecular level provides opportunities for identiﬁcation of key binding amino acids – valuable information for understanding pathological mechanisms and discovering novel drug targets. In the context of EOFAD, some of these APP mutations might be closely involved with such amino acids or might inﬂuence important structural regions involved in their protein-protein interface.These ﬁndings highlight the importance of further investigating the structural intricacies of APP and its interactions, oﬀering new avenues for understanding EOFAD pathogenesis and identifying potential therapeutic targets that could beneﬁt both rare and common forms of AD.
published_date	2026-01-30T05:32:43Z
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Bioinformatics investigation of the amyloid precursor protein and its interactions with presenilin-1 and acetylcholinesterase in early onset familial Alzheimer's disease / JOIC JACINTO

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