Pathological heterogeneity in progressive supranuclear palsy and corticobasal degeneration

Abstract

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are sporadic neurodegenerative disorders of late adult life. Focal asymmetric cortical atrophy with ballooned neurons, nigral degeneration, and tau-positive neuronal and glial lesions in both the gray and white matter, especially astrocytic plaques in the affected cerebral cortex, are characteristic features of CBD. While cortical involvement may occur in PSP, ballooned neurons are sparse and limited to the limbic system, and tufted astrocytes are abundant in the precentral gyrus and striatum. The present findings suggest that PSP and CBD are distinct pathological entities. However, there exist 'atypical' cases of PSP and CBD. Severe cortical involvement or asymmetric cortical atrophy can be seen in PSP. Ballooned neurons are sparse or difficult to detect in some cases of CBD, in spite of typical cortical tau pathology. Cortical symptoms are absent or only mild in 'minimal change' CBD. Moreover, several neurodegenerative disorders can underlie CBD. This pathological heterogeneity leads to difficulty in the clinical and pathological diagnosis of both disorders.

Intact coupling of M1 receptors and preserved M2 and M4 receptors in the cortex in progressive supranuclear palsy: Contrast with other dementias

“…There is only mild pathological involvement of the frontal cortex in PSP compared to subcortical structures. This may explain why cortical M1 receptors and their coupling to G proteins are normal (Wakabayashi and Takahashi, 2004), despite widespread subcortical cholinergic dysfunction in PSP, as shown in our previous work (Warren et al, 2007a,c). Subsets of cortical muscarinic receptors have not been measured previously in PSP although total muscarinic receptor in two post-mortem studies showed no difference between PSP and controls (Pascual et al, 1994;Ruberg et al, 1985).…”

Atypical association of semantic dementia, corticobasal syndrome, and 4R tauopathy

“…Neuropathological criteria of CBD comprise cortical degeneration in a peri-rolandic distribution, though atypical presentations are not uncommon, including the frontal lobe, peri-sylvian region, and medial temporal lobe (Dickson et al, 2002;Dickson, Kouri, Murray, & Josephs, 2011;Kouri, Murray, et al, 2011;Murray et al, 2007;Wakabayashi & Takahashi, 2004). Atypical cases of PSP with severe cortical involvement have also been reported in which atrophy of frontal, temporal, or parietal lobes has been observed (Dickson, Ahmed, Algom, Tsuboi, & Josephs, 2010;Wakabayashi & Takahashi, 2004).…”

“…Our patient's predominant temporal atrophy fits neither CBD, nor PSP. Microscopic features enable further distinction: CBD is characterized by greater cortical tau pathology, greater thread accumulation in white matter than PSP, and by the presence of astrocytic plaques which are considered the most specific histopathological feature of CBD (Dickson et al, 2002Forman et al, 2002;Wakabayashi & Takahashi, 2004;Williams & Lees, 2009). Ballooned neurons are not distinctive and their absence or rarity does not preclude the diagnosis of CBD (Dickson et al, 2002;Wakabayashi & Takahashi, 2004).…”

“…Microscopic features enable further distinction: CBD is characterized by greater cortical tau pathology, greater thread accumulation in white matter than PSP, and by the presence of astrocytic plaques which are considered the most specific histopathological feature of CBD (Dickson et al, 2002Forman et al, 2002;Wakabayashi & Takahashi, 2004;Williams & Lees, 2009). Ballooned neurons are not distinctive and their absence or rarity does not preclude the diagnosis of CBD (Dickson et al, 2002;Wakabayashi & Takahashi, 2004). 4R-tau-positive Pick body-like inclusions have already been associated with several conditions, including CBD and PSP (Armstrong, Cairns, & Lantos, 2000;Ikeda, Akiyama, Arai, & Tsushiya, 2002;Kovacs & Budka, 2010;Kovacs et al, 2012;Miki, Mori, Hori, Kaimori, & Wakabayashi, 2009).…”

Can neurodegenerative disease be defined by four ‘primary determinants’: anatomy, cells, molecules, and morphology?

“…Enlarged neurons are also present in CJD, especially in cases with severe white matter degeneration [17,96,104]. In PSP, however, EN are less numerous and where present confined to limbic regions [124,167]. There are also different types of EN.…”