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Cure of Alzheimer’s Dementia Requires Addressing All of the Affected Brain Cell Types

Multiple genetic, metabolic, and environmental abnormalities are known to contribute to the pathogenesis of Alzheimer’s dementia (AD). If all of those abnormalities were addressed it should be possible to reverse the dementia; however, that would require a suffocating volume of drugs. Nevertheless,...

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Autor principal: Fessel, Jeffrey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004473/
https://www.ncbi.nlm.nih.gov/pubmed/36902833
http://dx.doi.org/10.3390/jcm12052049
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author Fessel, Jeffrey
author_facet Fessel, Jeffrey
author_sort Fessel, Jeffrey
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description Multiple genetic, metabolic, and environmental abnormalities are known to contribute to the pathogenesis of Alzheimer’s dementia (AD). If all of those abnormalities were addressed it should be possible to reverse the dementia; however, that would require a suffocating volume of drugs. Nevertheless, the problem may be simplified by using available data to address, instead, the brain cells whose functions become changed as a result of the abnormalities, because at least eleven drugs are available from which to formulate a rational therapy to correct those changes. The affected brain cell types are astrocytes, oligodendrocytes, neurons, endothelial cells/pericytes, and microglia. The available drugs include clemastine, dantrolene, erythropoietin, fingolimod, fluoxetine, lithium, memantine, minocycline, pioglitazone, piracetam, and riluzole. This article describes the ways by which the individual cell types contribute to AD’s pathogenesis and how each of the drugs corrects the changes in the cell types. All five of the cell types may be involved in the pathogenesis of AD; of the 11 drugs, fingolimod, fluoxetine, lithium, memantine, and pioglitazone, each address all five of the cell types. Fingolimod only slightly addresses endothelial cells, and memantine is the weakest of the remaining four. Low doses of either two or three drugs are suggested in order to minimize the likelihood of toxicity and drug–drug interactions (including drugs used for co-morbidities). Suggested two-drug combinations are pioglitazone plus lithium and pioglitazone plus fluoxetine; a three-drug combination could add either clemastine or memantine. Clinical trials are required to validate that the suggest combinations may reverse AD.
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spelling pubmed-100044732023-03-11 Cure of Alzheimer’s Dementia Requires Addressing All of the Affected Brain Cell Types Fessel, Jeffrey J Clin Med Perspective Multiple genetic, metabolic, and environmental abnormalities are known to contribute to the pathogenesis of Alzheimer’s dementia (AD). If all of those abnormalities were addressed it should be possible to reverse the dementia; however, that would require a suffocating volume of drugs. Nevertheless, the problem may be simplified by using available data to address, instead, the brain cells whose functions become changed as a result of the abnormalities, because at least eleven drugs are available from which to formulate a rational therapy to correct those changes. The affected brain cell types are astrocytes, oligodendrocytes, neurons, endothelial cells/pericytes, and microglia. The available drugs include clemastine, dantrolene, erythropoietin, fingolimod, fluoxetine, lithium, memantine, minocycline, pioglitazone, piracetam, and riluzole. This article describes the ways by which the individual cell types contribute to AD’s pathogenesis and how each of the drugs corrects the changes in the cell types. All five of the cell types may be involved in the pathogenesis of AD; of the 11 drugs, fingolimod, fluoxetine, lithium, memantine, and pioglitazone, each address all five of the cell types. Fingolimod only slightly addresses endothelial cells, and memantine is the weakest of the remaining four. Low doses of either two or three drugs are suggested in order to minimize the likelihood of toxicity and drug–drug interactions (including drugs used for co-morbidities). Suggested two-drug combinations are pioglitazone plus lithium and pioglitazone plus fluoxetine; a three-drug combination could add either clemastine or memantine. Clinical trials are required to validate that the suggest combinations may reverse AD. MDPI 2023-03-04 /pmc/articles/PMC10004473/ /pubmed/36902833 http://dx.doi.org/10.3390/jcm12052049 Text en © 2023 by the author. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Perspective
Fessel, Jeffrey
Cure of Alzheimer’s Dementia Requires Addressing All of the Affected Brain Cell Types
title Cure of Alzheimer’s Dementia Requires Addressing All of the Affected Brain Cell Types
title_full Cure of Alzheimer’s Dementia Requires Addressing All of the Affected Brain Cell Types
title_fullStr Cure of Alzheimer’s Dementia Requires Addressing All of the Affected Brain Cell Types
title_full_unstemmed Cure of Alzheimer’s Dementia Requires Addressing All of the Affected Brain Cell Types
title_short Cure of Alzheimer’s Dementia Requires Addressing All of the Affected Brain Cell Types
title_sort cure of alzheimer’s dementia requires addressing all of the affected brain cell types
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10004473/
https://www.ncbi.nlm.nih.gov/pubmed/36902833
http://dx.doi.org/10.3390/jcm12052049
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