Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration

Abstract

Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration atypical cases are described that have overlapping clinical and pathologic features. Both PSP and CBD have similar biochemical alterations in the tau protein, with the abnormal tau protein containing predominantly four-repeat tau. While there is overlap in the pathology in PSP and CBD, there are sufficient differences to continue the present day trend to consider these separate disorders. Several important pathologic features differentiate PSP from CBD. Ballooned neurons are frequent and nearly a sine qua non for CBD, but they are found in PSP at a frequency similar to that of other neurodegenerative diseases, such as Alzheimer's disease. Astrocytic lesions are different, with tufted astrocytes found in motor cortex and striatum in PSP and astrocytic plaques in focal atrophic cortices in CBD. The most characteristic neuronal tau pathology in CBD is wispy, fine filamentous inclusions within neuronal cell bodies, while affected neurons in PSP have compact, dense filamentous aggregates characteristic of globose neurofibrillary tangles. Thread-like processes in gray and white matter are much more numerous and widespread in CBD than in PSP. The brunt of the pathology in CBD is in the cerebrum, while the basal ganglia, diencephalon and brainstem are the targets of PSP. Further clinicopathologic studies will refine our understanding of these disorders and open the possibility that common etiologic factors may be identified for these unusual sporadic tauopathies. Abstract Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are usually sporadic multisystem degenerations associated with filamentous tau inclusions in neurons and glia. As such they can be considered sporadic tauopathies in contrast to familial tauopathies linked to mutations in the tau gene. Mutations have not been found in the tau gene in either PSP or CBD. The clinical syndromes and neuroimaging of typical cases of PSP and CBD are distinct; however, Key words

TOC1: Characterization of a Selective Oligomeric Tau Antibody

“…This indicates that the TOC1 antibody may prove a powerful tool for tauopathy characterization. Although largely labeling neuropil threads and pretangle neurons in AD, TOC1 reactivity demonstrates the characteristic astrocytic plaques or “crown of thorns” morphology in CBD; similarly PSP tissue reactivity indicated the presence of tufted astrocytes, the pathognomonic structures characteristic of this disease [10]. Since TOC1 is reactive in multiple tauopathies, its reactivity must depend on the appearance of a conformation common to the three diseases assayed.…”

“…However we now know that tau pathology is more closely correlated with cognitive decline [6] and that mutations in tau alone can cause neurode-generation [7–9]. Additionally, sporadic tauopathies such as corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), though not caused by autosomal dominant mutations in the tau gene [10], are nonetheless characterized by tau protein misfolding much the same as that which occurs in AD and familial tauopathies. Moreover, in each of these diseases, the misfolded tau is hyperphosphorylated, although the location and morphology of the tau inclusions vary with the disease state [11].…”

Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases

“…For example, among the various tauopathies characterized by the accumulation of tau aggregates (for example, Alzheimer’s disease, argyrophilic grain disease, progressive supranuclear palsy, corticobasal degeneration and Pick’s disease), there are substantial variations in clinical symptoms, age of disease onset, rate of progression, types of cells affected (neurons and/or glial cells), brain region–specific distribution of tau inclusions and morphology of tau tangles 113,114 . At the same time, considerable overlap occurs among different categories of diseases, in both clinical symptoms 115,116 and neuropathologies, whereby different protein aggregates such as NFTs and Lewy bodies frequently co-deposit in diseased brains 117 .…”

Is synaptic loss a unique hallmark of Alzheimer's disease?

“…From a neuropathologic perspective, there are numerous NFT in both the basal ganglia and the brainstem and it is common to observe NFT in the motor and parietal areas. Neuronal loss is often observed in the frontal and parietal cortex accompanied by increased microglial activation [131–134]. Bigio et al [135] hypothesized that frontal cortex would show synaptic loss in individuals with PSP and dementia while individuals with only PSP would not.…”