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A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons
Prevention is better than cure and prevention of Alzheimer's disease (AD) may be possible. In elderly persons who are cognitively normal, synaptic hypometabolism as shown by reduced cerebral uptake of fluorodeoxyglucose ((18)F‐FDG), provides a premonitory signal of potential, future loss of cog...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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John Wiley and Sons Inc.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864087/ https://www.ncbi.nlm.nih.gov/pubmed/33598529 http://dx.doi.org/10.1002/trc2.12126 |
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author | Fessel, Jeffrey |
author_facet | Fessel, Jeffrey |
author_sort | Fessel, Jeffrey |
collection | PubMed |
description | Prevention is better than cure and prevention of Alzheimer's disease (AD) may be possible. In elderly persons who are cognitively normal, synaptic hypometabolism as shown by reduced cerebral uptake of fluorodeoxyglucose ((18)F‐FDG), provides a premonitory signal of potential, future loss of cognition if those individuals also have present evidence of amyloid deposition seen in the Pittsburgh compound B positron emission tomography (PIB‐PET) scan for amyloid. Those are the persons who should be targeted if one aims to prevent AD. The synaptic hypometabolism implies that the brain's availability of adenosine triphosphate (ATP) is inadequate for performance of all required synaptic functions. This review first describes the basis for asserting that reduced cerebral uptake of (18)F‐FDG accurately reflects synaptic hypometabolism; second, explains the basis for asserting that hypometabolism implies inadequate ATP; third, shows that amyloid beta (Aβ) itself, Aβ modified by pyroglutamate to become a molecule termed pE(3)Aβ, and cyclophilin‐D, in concert are the main contributors to inadequate synaptic ATP and that, therefore, reducing all of their levels would neutralize their combined effect and correct the hypometabolism. pE(3)Aβ is more neurotoxic than unmodified Aβ; and cyclophilin D inhibits ATP synthase and reduces ATP formation. Finally, this review describes an mRNA self‐replicating vaccine that will raise brain levels of ATP by reducing Aβ, pyroglutamate‐modified Aβ, and cyclophilin‐D, and thereby—in cognitively normal elderly persons who have synaptic hypometabolism—prevent initiation of the process that terminates in AD. |
format | Online Article Text |
id | pubmed-7864087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78640872021-02-16 A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons Fessel, Jeffrey Alzheimers Dement (N Y) Perspective Prevention is better than cure and prevention of Alzheimer's disease (AD) may be possible. In elderly persons who are cognitively normal, synaptic hypometabolism as shown by reduced cerebral uptake of fluorodeoxyglucose ((18)F‐FDG), provides a premonitory signal of potential, future loss of cognition if those individuals also have present evidence of amyloid deposition seen in the Pittsburgh compound B positron emission tomography (PIB‐PET) scan for amyloid. Those are the persons who should be targeted if one aims to prevent AD. The synaptic hypometabolism implies that the brain's availability of adenosine triphosphate (ATP) is inadequate for performance of all required synaptic functions. This review first describes the basis for asserting that reduced cerebral uptake of (18)F‐FDG accurately reflects synaptic hypometabolism; second, explains the basis for asserting that hypometabolism implies inadequate ATP; third, shows that amyloid beta (Aβ) itself, Aβ modified by pyroglutamate to become a molecule termed pE(3)Aβ, and cyclophilin‐D, in concert are the main contributors to inadequate synaptic ATP and that, therefore, reducing all of their levels would neutralize their combined effect and correct the hypometabolism. pE(3)Aβ is more neurotoxic than unmodified Aβ; and cyclophilin D inhibits ATP synthase and reduces ATP formation. Finally, this review describes an mRNA self‐replicating vaccine that will raise brain levels of ATP by reducing Aβ, pyroglutamate‐modified Aβ, and cyclophilin‐D, and thereby—in cognitively normal elderly persons who have synaptic hypometabolism—prevent initiation of the process that terminates in AD. John Wiley and Sons Inc. 2021-02-05 /pmc/articles/PMC7864087/ /pubmed/33598529 http://dx.doi.org/10.1002/trc2.12126 Text en © 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Perspective Fessel, Jeffrey A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons |
title | A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons |
title_full | A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons |
title_fullStr | A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons |
title_full_unstemmed | A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons |
title_short | A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons |
title_sort | vaccine to prevent initial loss of cognition and eventual alzheimer's disease in elderly persons |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864087/ https://www.ncbi.nlm.nih.gov/pubmed/33598529 http://dx.doi.org/10.1002/trc2.12126 |
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