However in the terms of Izaks and Westendorp infection inflammation is a component cause, but not a sufficient cause. There are undoubtedly good reasons to suspect that a systemic age related component so far unidentified contributes Erlotinib purchase to both diseases. This is an exciting area of research, and one hopes that the next years will bring a new understanding of why some individuals develop AD, others ATH, whereas many avoid both conditions. There are implications for drug development, and drugs with moderate efficacy in either ATH or AD warrant testing in the other disorder. Further research will be necessary to unravel the mo lecular underpinnings that link infection, oxysterols, and the age relatedness of these two major diseases.
Background Better nutrition and lifestyle changes make important contributions to extending human lifespan, but new morbidities are encountered with aging, notably AD and ATH. At first sight these appear to be different Inhibitors,Modulators,Libraries condi tions. In the present debate we address whether the two conditions are different, or instead share a common etiology. We build upon a previous debate Ill or Just Old and agree with Izaks and Westendorp that we should investigate the risk factors of diseases in the latter part of life. The discussion here commences with age related risk factors, genetic predis positions, animal models, and the Inhibitors,Modulators,Libraries central involvement of the vasculature Inhibitors,Modulators,Libraries and inflammation. We then extend the discussion to infection, amyloid B, animal models, infec tion, drugs, and the central signaling role of cholesterol derivatives.
We suggest that both conditions result Inhibitors,Modulators,Libraries from an inflammatory disorder as a result of an infectious condition, both crucially linked to sterol metabolism and innate immunity, leading to vascular occlusion. Discussion Disease characteristics AD is the main form of dementia in Western countries, and is characterized by the presence in post mortem brain of extracellular amyloid plaques composed of AB generated by the aggregation of toxic peptide fragments of the Alzheimer precursor protein, APP, and intraneuronal deposition of highly phosphorylated filamentous aggregates of the microtubule associated protein Tau. Onset is typic ally above age 70.
By contrast, ATH, also known as arteriosclerotic vascular disease, is Inhibitors,Modulators,Libraries not a unitary disorder, and instead ranges from primary arterial atheroma in flammation and accumulation of cholesterol laden mac rophages in the walls of major arteries to plaque formation and inflammation in http://www.selleckchem.com/products/mek162.html the arterial wall, lead ing to progressive occlusion, with consequent risk of myocardial infarction or cerebral stroke because plaque rupture can provoke thrombosis. Disease development is accompanied by disruption of the endothelial cell layer, vascular smooth muscle cell migration, and matrix calcifi cation.