A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons
Abstract 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 (18F‐FDG), provides a premonitory signal of potential, future loss...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
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| Online Access: | https://doi.org/10.1002/trc2.12126 |
| _version_ | 1798023217511661568 |
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| author | Jeffrey Fessel |
| author_facet | Jeffrey Fessel |
| author_sort | Jeffrey Fessel |
| collection | DOAJ |
| description | Abstract 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 (18F‐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 18F‐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. |
| first_indexed | 2024-04-11T17:42:49Z |
| format | Article |
| id | doaj.art-e8b53c2e3b6c4c43afa06d6e84686e45 |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-04-11T17:42:49Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-e8b53c2e3b6c4c43afa06d6e84686e452022-12-22T04:11:27ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372021-01-0171n/an/a10.1002/trc2.12126A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly personsJeffrey Fessel0Department of Medicine University of California, San Francisco San Francisco California USAAbstract 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 (18F‐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 18F‐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.https://doi.org/10.1002/trc2.12126AbetaATP‐synthasecyclophilin‐Dinadequate ATP levelmRNA vaccine to prevent original cognitive lossnormal cognition |
| spellingShingle | Jeffrey Fessel A vaccine to prevent initial loss of cognition and eventual Alzheimer's disease in elderly persons Alzheimer’s & Dementia: Translational Research & Clinical Interventions Abeta ATP‐synthase cyclophilin‐D inadequate ATP level mRNA vaccine to prevent original cognitive loss normal cognition |
| 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 | Abeta ATP‐synthase cyclophilin‐D inadequate ATP level mRNA vaccine to prevent original cognitive loss normal cognition |
| url | https://doi.org/10.1002/trc2.12126 |
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