selleck products Resistance to Alzheimer’s disease This review has so far considered mainly changes that occur in the brain with normal ageing. Although there are some investigators who prefer to consider AD as distinct from ageing, we believe that there may be more advantages in regarding it as part of the spectrum of change that occurs in the brain with age. This approach is borne out by the enhanced associations that have been found of pathology with AD genetic susceptibility alleles if analyses involve not only neuropathological cases of definite AD but also other elderly cases with less marked AD pathology, referred to in the study by Bennett and colleagues [35] as ‘intermediate phenotypes’. This was also the approach to linking neuropathological variables and a range of cognitive scores in elderly subjects that was taken by Dowling and colleagues [4].

There are so many changes that are seen to a severe degree in definite AD and to a milder degree in normal ageing that this ‘intermediate phenotype’ model seems to make eminent sense. These include evidence in the brain of oxidative and other free radical damage, reduced anti-oxidative capacity, loss of synapses, expression of cell division cycle markers and neurons displaying hyperploidy, to name but a few. It is acknowledged that there may be step-wise blips within a spectrum of age-related changes encompassing AD that may influence cognitive performance and be marked by particular pathological changes, as suggested by Herrup Brefeldin_A [36].

Nevertheless, in the rest of this review, in which we consider what may constitute selleck bio ‘resistance’ to AD, we shall follow this ‘intermediate phenotype’ approach and include ‘resistance to brain ageing’. Factors that may protect an individual from progressing to the AD end of the spectrum of possible change as they age are legion. A recent review considered seven modifiable risk factors for AD and calculated that up to half of cases of AD might be attributable to such factors: diabetes, midlife hypertension, midlife obesity, smoking, depression, cognitive inactivity or low educational attainment and physical activity [37]. These factors are derived mainly from epidemiological studies and not from interventional studies, which at present remain inadequate [38]. These can be classified according to whether they are thought to act by strengthening brain reserve before it is assaulted by the effects of age on the one hand and those that constitute a reaction to such assaults on the other. It is beyond the scope of this review to examine these factors in detail but we shall give them brief consideration here.