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 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.