FIGURE 14.

Schematic illustration for a three-staged spatiotemporal progression of sorfra plaques in the cerebrum relative to Thal and Braak staging of β-amyloid and neurofibrillary tangle pathologies. The yellow areas, that is, hippocampal formation, primary motor (areas 4, 6) and somatosensory (areas 3, 1, 2) cortices, and striate cortex (area 17), highlight the neuroanatomical regions wherein the occurrence of neuropathology can define transition between the pathological stages. The upper half of the figure shows the regional distributions of sorfra plaques (represented by green dots) at the three stages, mapped in perspective of the lateral and medial cerebral surfaces, and frontal sectional view at the midhippocampal level, respectively. The low-left group of maps shows the regional distribution of β-amyloidosis (red dots) according to a modified (three-staged) version of the original five-phase Thal Aβ staging (Thal et al., 2002; Serrano-Pozo et al., 2011). The low-right group of maps shows the regional distribution of NFT/tauopathy (blue dots) according to a modified (also three-staged) version of the original Braak six-stage classification (Braak and Braak, 1991; Braak et al., 2006; Montine et al., 2012). The onset of sorfra plaque formation appears to occur along with β-amyloidosis in cerebral neocortex. However, the former is much restricted to the basal associative neocortex, whereas the latter develop over broader neocortical regions in the temporal, frontal, and occipital lobes. From Thal Aβ phase 2 and onward, β-amyloidosis progresses with an increase in the overall amount in the isocortical and allocortical cortex and hippocampal formation and also appears in subcortical structures. On the other hand, sorfra plaques develop in the limbic structures, extend over the associative neocortex, and finally invade the primary neocortical areas, along with the increase of plaque quantity. However, sorfra plaques essentially do not develop in the subcortical structures. In comparison with NFT pathogenesis, sorfra plaques do not develop in the brains with PART. The regional propagation of sorfra plaque formation in the brains with NFT at and above Braak stage III resembles the spatial trajectory of the development of tauopathy. Thus, both lesions extend from inferior to superior gyri in the associative neocortices and expand from the associative to primary neocortical functional areas. However, in temporal order, sorfra plaque pathogenesis precedes tauopathy in the associative and primary neocortical regions. In addition, in contrast to tauopathy, sorfra plaques do not develop in the subcortical regions.