Ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's disease

Abstract After the midninth decade of age, the incidence rates of Alzheimer's disease (AD) and the presence of active TGF‐β1 show comparable increases. The hypothesis is proposed that the reason why advanced age is a major risk factor for AD is a progressive decrease with advancing age in the n...

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Main Author: Jeffrey Fessel
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Alzheimer’s & Dementia: Translational Research & Clinical Interventions
Online Access:https://doi.org/10.1016/j.trci.2019.11.007
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author Jeffrey Fessel
author_facet Jeffrey Fessel
author_sort Jeffrey Fessel
collection DOAJ
description Abstract After the midninth decade of age, the incidence rates of Alzheimer's disease (AD) and the presence of active TGF‐β1 show comparable increases. The hypothesis is proposed that the reason why advanced age is a major risk factor for AD is a progressive decrease with advancing age in the numbers of TGFR2 receptors in the brain, with the consequence of a decline in the neurotrophic efficacy of TGF‐β1 and 2 despite their already increased levels in older persons. Alternative, possible reasons are discussed but rejected because either those reasons may also affect young persons or because they cannot be validated in a clinical trial. The proposed hypothesis may be validated in persons with aMCI after raising their brain levels of TGF‐β1 and 2 by using a combination of three drugs, lithium, memantine, plus either glatiramer or venlafaxine, and then assessing their progression to AD.
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series Alzheimer’s & Dementia: Translational Research & Clinical Interventions
spelling doaj-art-db351deb688a4592b265e0a89586cf6f2025-08-20T03:22:00ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372019-01-015189990510.1016/j.trci.2019.11.007Ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's diseaseJeffrey Fessel0Emeritus Department of MedicineUniversity of CaliforniaSan FranciscoSan FranciscoCAUSAAbstract After the midninth decade of age, the incidence rates of Alzheimer's disease (AD) and the presence of active TGF‐β1 show comparable increases. The hypothesis is proposed that the reason why advanced age is a major risk factor for AD is a progressive decrease with advancing age in the numbers of TGFR2 receptors in the brain, with the consequence of a decline in the neurotrophic efficacy of TGF‐β1 and 2 despite their already increased levels in older persons. Alternative, possible reasons are discussed but rejected because either those reasons may also affect young persons or because they cannot be validated in a clinical trial. The proposed hypothesis may be validated in persons with aMCI after raising their brain levels of TGF‐β1 and 2 by using a combination of three drugs, lithium, memantine, plus either glatiramer or venlafaxine, and then assessing their progression to AD.https://doi.org/10.1016/j.trci.2019.11.007
spellingShingle Jeffrey Fessel
Ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's disease
Alzheimer’s & Dementia: Translational Research & Clinical Interventions
title Ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's disease
title_full Ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's disease
title_fullStr Ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's disease
title_full_unstemmed Ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's disease
title_short Ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's disease
title_sort ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for alzheimer s disease
url https://doi.org/10.1016/j.trci.2019.11.007
work_keys_str_mv AT jeffreyfessel ineffectivelevelsoftransforminggrowthfactorsandtheirreceptoraccountforoldagebeingariskfactorforalzheimersdisease