120 Experiments in cell cultures and mouse models of AD suggest that folic acid deficiency and homocysteine impair DNA repair in neurons, which exposes them to oxidative damage

induced by amyloid.121 Finally, in addition to the independent, role of promoting AD pathology, all the risk factors presented above share the ability to promote atherosclerosis.122 This raises the question of whether atherosclerosis itself is the final common pathway through which they are involved in the pathogenesis of AD. Supporting this possibility is a population-based study of newly diagnosed demented patients, in which #Go-6983 keyword# the frequency of AD and VD was correlated with the severity of atherosclerosis. The odds ratio for AD in those with severe Inhibitors,research,lifescience,medical atherosclerosis compared with those without was 3.0. This association was stronger for those affected by atherosclerosis who were also ApoE4 carriers.36 An alternative explanation for these results could be that dementia causes an aggravation of atherosclerosis by alteration in lifestyle and diet. Conclusion The data presented above lend themselves to several interpretations. It is possible that, “pure” Inhibitors,research,lifescience,medical neurohistological vascular or “pure” plaques and/or

tangles dementias constitute the extreme and rare end of a continuous process. In fact, a significant proportion of dementia cases present vascular lesions upon neurohistological examination – the location, extent, and clinical implications of which depend on the damaged vessel, and the insidious formation of plaques and tangles.27 The cooccurrence of two pathological processes acting in parallel damages brain tissue, which, in turn, leads to a threshold of brain dysfunction Inhibitors,research,lifescience,medical viewed as clinical symptoms.25 It is thus conceivable that

cerebrovascular damage is caused in individuals affected in midlife by vascular risk factors, which later joins progressive and age-dependent formation Inhibitors,research,lifescience,medical of amyloid plaques, thus damaging brain tissue and being expressed as dementia. Conceptually, this would not be different, from other aging processes leading to organ failure via several, concomitant processes, such as cardiac failure due to coronary ischemia and valvulopathy, or leading to functional failure, such as visual failure due to concomitant cataract and retinopathy. Alternatively, rather than PD184352 (CI-1040) comorbidity of VD and ADtype dementia, part of the AD pathological pathway could involve a vascular component, in which impairment of blood-brain barrier leads to disruption of selective permeability (by altering endothelial functioning), which, in turn, stimulates plaque and tangle formation. An additional option for the conceptualization of the role of risk factors discussed above, and of other risk factors in AD, is that AD is a complex, multifactorial disease.