Fig. 5.

Summary diagram of four regional distribution patterns of pathology in bvFTLD illustrating the hypothesis that pTDP-43 pathology may spread sequentially, possibly propagating (white arrows) along axonal pathways. Preferentially vulnerable cortical and subcortical sites are involved. Pattern I cases with the lowest burden of pTDP pathology display the presence of pTDP-43 immunoreactive inclusions in projection neurons and oligodendrocytes of basal and anterior portions of the prefrontal neocortex (orbital gyri, gyrus rectus, inferior frontal gyrus). Pattern II cases show the same lesion distribution as pattern I, but with pTDP pathology also in prefrontal neocortical areas located further caudal to the frontal pole, including the middle frontal gyrus, insular cortex, and anterior cingulate gyrus, and also in anteromedial areas (transentorhinal region, adjoining allocortical entorhinal region and hippocampal formation), the superior and middle temporal gyri, striatum (accumbens nucleus, putamen, claustrum), parvocellular portion of the red nucleus, medial and lateral portions of the thalamus, and in precerebellar nuclei of the pons and medulla oblongata. Cases with additional pathology beyond that seen in the first two patterns are characterized by the presence of pTDP-43 immunoreactive inclusions in the agranular motor neocortex (Brodmann fields 4 and 6), in parietal neocortical areas (sensory cortex, angular gyrus), in bulbar somatomotor neurons, and in α-motoneruons of the cervical spinal cord anterior horns which is pattern III. Cases with the highest burden of pathology (pattern IV) show the presence of pTDP-43 lesions in the occipital neocortex (visual cortex, Brodmann 17, 18) in addition to involvement of all of the areas involved in patterns I–III. a pc precerebellar nuclei; c XII hypoglossal nucleus, io inferior olive; e ca caudate nucleus, pu putamen, pi internal pallidum, pe external pallidum, fo fornix, cl claustrum, mc mediocentral subnuclei of the bl basolateral subnuclei of amygdala, en entorhinal cortex (en); f pu putamen, md mediodorsal thalamus, rn red nucleus, sn substantia nigra (sn), ca1 Ammon's horn region 1, en entorhinal cortex