More severe medial-temporal lobe atrophy may be present in symptomatic ADAD carriers compared with SAD [37]. Gray-matter regional volume loss and decreases in magnetization transfer ratio have also been reported in mildly selleck products symptomatic carriers [38]. Longitudinal structural imaging studies have demonstrated an accelerated course of atrophy compared with SAD, in both regional-medial temporal lobe and whole-brain measures [39-41] and in cortical thinning, particularly evident in the precuneus and posterior cingulate prior to the diagnosis of dementia [42]. Alterations in white matter structure have also been demonstrated in presymptomatic and early symptomatic carriers, with decreased fractional anisotropy in the fornix and widespread areas of brain visualized with diffusion tensor imaging [43].

Presymptomatic alterations in brain perfusion and metabolism, similar to the patterns reported in SAD, have also been reported among ADAD carriers using nuclear medicine techniques, including single photon emission tomography [44,45] and positron emission tomography (PET) [46,47]. One study demonstrated early glucose fluorodeoxyglucose-PET hypometabolism in the posterior cingulate cortices, hippocampus and entorhinal cortices of presymptomatic carriers of ADAD mutations, which was present prior to significant atrophy in these regions [48]. Functional MRI techniques have demonstrated alterations in hippocampal activity during episodic memory tasks in presymptomatic ADAD carriers that appear to occur decades prior to dementia [49], similar to the observations in young apolipoprotein E ??4 carriers [50,51], however, this observation was not replicated in a larger population of ADAD mutation carriers in a study employing an implicit novelty encoding paradigm [52].

More recently, PET amyloid imaging studies with Pittsburgh Compound B (PiB) have revealed evidence of fibrillar A?? deposition in ADAD, including carriers who were up to 10 years younger than the age of onset for their family [53-55]. Interestingly, these studies have Carfilzomib consistently reported elevated levels of PiB retention in the striatum of presymptomatic ADAD individuals, which occurs more variably in late-onset SAD. Biomarkers The biochemical changes in the selleck bio brain, cerebrospinal fluid (CSF) and blood of persons with AD have been described in detail over the past 30 years. Many biochemical changes in the brain have been documented to occur in the AD process, with those biomarkers associated with amyloid plaques and neurofibrillary tangles being specific for pathologically defined AD [6,56]. The identification of A?? as the major component of CAA [57] and amyloid deposits in plaques [58] was followed by the finding that tau is the major component of neurofibrillary tangles.