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Wang J, Ho L, Chen L, Zhao Z, Zhao W, Qian X, Humala N, Seror I, Bartholomew S, Rosendorff C, Pasinetti GM. Valsartan lowers brain beta-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease. J Clin Invest. 2007 Nov;117(11):3393-402. PubMed.
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Perhaps the effect that is being seen is related to C-reactive protein. CRP is clearly implicated in Alzheimer's, and apparently valsartan reduces CRP.
Here are a few quotes to illustrate:
"Inflammation plays an important role in the pathogenesis of Alzheimer's disease.... [T]he level of systemic inflammation markers, particularly C-reactive protein and interleukin-6, can predict cognitive decline or dementia.” (1)
"Blood levels of CRP... are associated with higher risk of Alzheimer disease and cognitive decline during aging.” (2)
"C-reactive protein has been shown to co-deposit with C fragments in a number of disorders, including Alzheimer's disease..." (3)
"Angiotensin receptor blockers (ARBs) (valsartan, irbesartan, olmesartan, telmisartan) markedly reduce serum levels of CRP." (4)
References:
Dziedzic T. Systemic inflammatory markers and risk of dementia. Am J Alzheimers Dis Other Demen. 2006 Aug-Sep;21(4):258-62. PubMed.
Finch CE, Morgan TE. Systemic inflammation, infection, ApoE alleles, and Alzheimer disease: a position paper. Curr Alzheimer Res. 2007 Apr;4(2):185-9. PubMed.
Klegeris A, Singh EA, McGeer PL. Effects of C-reactive protein and pentosan polysulphate on human complement activation. Immunology. 2002 Jul;106(3):381-8. PubMed.
Prasad K. C-reactive protein (CRP)-lowering agents. Cardiovasc Drug Rev. 2006 Spring;24(1):33-50. PubMed.
View all comments by P.F. JenningsDarmstadt Technical University
The analysis of the pleitropic effects of Valsartan is striking. The potential of a class effect amongst the sartan drug family should be investigated further. Several of the inactive compounds in the first assay round are not the real Valsartan competing agent: Losartan (a primary alcohol) is active as its acidic metabolite EXP3174; Candesartan Cilexitil is a prodrug, which requires metabolic activation.
Tasosartan, Telmisartan and Irbesartan lack a crucial acid moiety common to the other three.
References:
Schmidt B, Schieffer B. Angiotensin II AT1 receptor antagonists. Clinical implications of active metabolites. J Med Chem. 2003 Jun 5;46(12):2261-70. PubMed.
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