Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model

Alzheimer’s disease (AD) is a neurodegenerative disease caused by abnormal functioning of critical physiological processes in nerve cells and aberrant accumulation of protein aggregates in the brain. The initial cause remains elusive—the only unquestionable risk factor for the most frequent variant...

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Autores principales:	Guido Santos, Mario Díaz
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Alzheimer disease Braak stages neuropathology lipid rafts lipid composition mathematical modeling Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/7fd108b350c645f4890051922ffa9da9
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spelling	oai:doaj.org-article:7fd108b350c645f4890051922ffa9da92021-11-25T17:54:04ZDimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model10.3390/ijms2222121811422-00671661-6596https://doaj.org/article/7fd108b350c645f4890051922ffa9da92021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12181https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Alzheimer’s disease (AD) is a neurodegenerative disease caused by abnormal functioning of critical physiological processes in nerve cells and aberrant accumulation of protein aggregates in the brain. The initial cause remains elusive—the only unquestionable risk factor for the most frequent variant of the disease is age. Lipid rafts are microdomains present in nerve cell membranes and they are known to play a significant role in the generation of hallmark proteinopathies associated to AD, namely senile plaques, formed by aggregates of amyloid β peptides. Recent studies have demonstrated that human brain cortex lipid rafts are altered during early neuropathological phases of AD as defined by Braak and Braak staging. The lipid composition and physical properties of these domains appear altered even before clinical symptoms are detected. Here, we use a coarse grain molecular dynamics mathematical model to predict the dimensional evolution of these domains using the experimental data reported by our group in human frontal cortex. The model predicts significant size and frequency changes which are detectable at the earliest neuropathological stage (ADI/II) of Alzheimer’s disease. Simulations reveal a lower number and a larger size in lipid rafts from ADV/VI, the most advanced stage of AD. Paralleling these changes, the predictions also indicate that non-rafts domains undergo simultaneous alterations in membrane peroxidability, which support a link between oxidative stress and AD progression. These synergistic changes in lipid rafts dimensions and non-rafts peroxidability are likely to become part of a positive feedback loop linked to an irreversible amyloid burden and neuronal death during the evolution of AD neuropathology.Guido SantosMario DíazMDPI AGarticleAlzheimer diseaseBraak stagesneuropathologylipid raftslipid compositionmathematical modelingBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12181, p 12181 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Alzheimer disease Braak stages neuropathology lipid rafts lipid composition mathematical modeling Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Alzheimer disease Braak stages neuropathology lipid rafts lipid composition mathematical modeling Biology (General) QH301-705.5 Chemistry QD1-999 Guido Santos Mario Díaz Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model
description	Alzheimer’s disease (AD) is a neurodegenerative disease caused by abnormal functioning of critical physiological processes in nerve cells and aberrant accumulation of protein aggregates in the brain. The initial cause remains elusive—the only unquestionable risk factor for the most frequent variant of the disease is age. Lipid rafts are microdomains present in nerve cell membranes and they are known to play a significant role in the generation of hallmark proteinopathies associated to AD, namely senile plaques, formed by aggregates of amyloid β peptides. Recent studies have demonstrated that human brain cortex lipid rafts are altered during early neuropathological phases of AD as defined by Braak and Braak staging. The lipid composition and physical properties of these domains appear altered even before clinical symptoms are detected. Here, we use a coarse grain molecular dynamics mathematical model to predict the dimensional evolution of these domains using the experimental data reported by our group in human frontal cortex. The model predicts significant size and frequency changes which are detectable at the earliest neuropathological stage (ADI/II) of Alzheimer’s disease. Simulations reveal a lower number and a larger size in lipid rafts from ADV/VI, the most advanced stage of AD. Paralleling these changes, the predictions also indicate that non-rafts domains undergo simultaneous alterations in membrane peroxidability, which support a link between oxidative stress and AD progression. These synergistic changes in lipid rafts dimensions and non-rafts peroxidability are likely to become part of a positive feedback loop linked to an irreversible amyloid burden and neuronal death during the evolution of AD neuropathology.
format	article
author	Guido Santos Mario Díaz
author_facet	Guido Santos Mario Díaz
author_sort	Guido Santos
title	Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model
title_short	Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model
title_full	Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model
title_fullStr	Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model
title_full_unstemmed	Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model
title_sort	dimensional changes in lipid rafts from human brain cortex associated to development of alzheimer’s disease. predictions from an agent-based mathematical model
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/7fd108b350c645f4890051922ffa9da9
work_keys_str_mv	AT guidosantos dimensionalchangesinlipidraftsfromhumanbraincortexassociatedtodevelopmentofalzheimersdiseasepredictionsfromanagentbasedmathematicalmodel AT mariodiaz dimensionalchangesinlipidraftsfromhumanbraincortexassociatedtodevelopmentofalzheimersdiseasepredictionsfromanagentbasedmathematicalmodel
_version_	1718411870903205888

Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model

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