The ASYMAD group showed Selleck GSK458 longitudinal increases in rCBF in the anterior insula, hippocampus and parahippocampal gyrus relative to both CI and CN groups. These functional differences occurred even though all three groups had similar Braak scores, indicating similar amounts of tau in the medial temporal lobe. The fact that ASYMAD, CI, and CN groups have tau in the medial temporal lobe argues against increased rCBF in response to the presence neuropathology alone. Instead, previous evidence of neuronal plasticity from Inhibitors,research,lifescience,medical other cases from the BLSA may support these functional differences. It has been shown that hippocampal neurons exhibit hypertrophy
of the cell
body, nucleus, and nucleolus in ASYMAD that is not observed in individuals with MCI or AD (Riudavets et al. 2007; Iacono et al. 2008; Iacono et al. 2009a); a finding that has been replicated in cases from the Nun Study (Riudavets et al. 2007; Iacono Inhibitors,research,lifescience,medical et al. 2008; Iacono et al. 2009a). Furthermore, in the neurons of ASYMAD there is increased expression of cyclins (M. Riudavets, unpubl. ms.) and of mRNA for multiple synaptic proteins Inhibitors,research,lifescience,medical (Iacono et al. 2009b). Together, these cellular and brain activity changes suggest the possibility of compensatory processes in ASYMAD subjects that may contribute to cognitive resilience in the face of substantial AD pathology. The CI group, conversely, showed decreased rCBF in several regions relative to ASYMAD and CN. These included rCBF declines in the anterior and posterior cingulate, the cuneus, Inhibitors,research,lifescience,medical and the brainstem. Previous studies lend support to these findings, in that Inhibitors,research,lifescience,medical these regions show early metabolic decreases in AD (Mosconi 2005), and rCBF in the posterior cingulate cortex correlates with Braak NFT scores (Bradley et al. 2002). In terms of function, the cingulate regions are thought to participate in higher
order cognitive functions (Binder et al. 2009; Medford and Critchley 2010) and have also been implicated in the default mode network of resting state brain activity (Shulman et al. 1997; Buckner and Vincent 2007), the disruption of which may impact cognitive ability in the aging brain (Lustig et al. 2003; Grady et al. 2006). Together, these declines in brain activity may be related to the decline in cognitive function that Molecular Cell ultimately occurred in the impaired group. The differential patterns of rCBF between the ASYMAD and CI groups are intriguing since they occurred in groups with similar pathologic features but divergent clinical outcomes. However, due to the small size of the study group, it is possible that we were not able to detect a difference in the amount of tau or amyloid between the CI and ASYMAD subjects.