Subcortical neurodegeneration in chorea: Similarities and differences between chorea-acanthocytosis and Huntington's disease.

INTRODUCTION: Chorea-acanthocytosis (ChAc) and Huntington's disease (HD) are neurodegenerative conditions that share clinical and neuropathological features, despite their distinct genetic etiologies. METHODS: In order to compare these neuropathologies, serial gallocyanin-stained brain sections from three subjects with ChAc were analyzed and compared with our previous studies of eight HD cases, in addition to three hemispheres from two male controls. RESULTS: Astrogliosis was much greater in the ChAc striatum, as compared to that found in HD, with dramatic increase in total striatal glia numbers and the number of glia per striatal neuron. Striatal astrocytes are most likely derived from the striatal subependymal layer in ChAc, which showed massive proliferation. The thalamic centromedian-parafascicular complex is reciprocally connected to the striatum and is more heavily affected in HD than in ChAc. CONCLUSION: The distinct patterns of selective vulnerability and gliosis observed in HD and ChAc challenge simplistic views on the pathogenesis of these two diseases with rather similar clinical signs. The particular roles played by astroglia in ChAc and in HD clearly need to be elucidated in more detail.

Hierarchical Distribution of the Tau Cytoskeletal Pathology in the Thalamus of Alzheimer's Disease Patients.

In spite of considerable progress in neuropathological research on Alzheimer's disease (AD), knowledge regarding the exact pathoanatomical distribution of the tau cytoskeletal pathology in the thalamus of AD patients in the advanced Braak and Braak AD stages V or VI of the cortical cytoskeletal pathology is still fragmentary. Investigation of serial 100 µm-thick brain tissue sections through the thalamus of clinically diagnosed AD patients with Braak and Braak AD stage V or VI cytoskeletal pathologies immunostained with the anti-tau AT8 antibody, along with the affection of the extraterritorial reticular nucleus of the thalamus, reveals a consistent and severe tau immunoreactive cytoskeletal pathology in the limbic nuclei of the thalamus (e.g., paraventricular, anterodorsal and laterodorsal nuclei, limitans-suprageniculate complex). The thalamic nuclei integrated into the associative networks of the human brain (e.g., ventral anterior and mediodorsal nuclei) are only mildly affected, while its motor precerebellar (ventral lateral nucleus) and sensory nuclei (e.g., lateral and medial geniculate bodies, ventral posterior medial and lateral nuclei, parvocellular part of the ventral posterior medial nucleus) are more or less spared. The highly stereotypical and characteristic thalamic distribution pattern of the AD-related tau cytoskeletal pathology represents an anatomical mirror of the hierarchical topographic distribution of the cytoskeletal pathology in the interconnected regions of the cerebral cortex of AD patients. These pathoanatomical parallels support the pathophysiological concept of a transneuronal spread of the disease process of AD along anatomical pathways. The AD-related tau cytoskeletal pathology in the thalamus most likely contributes substantially to the neuropsychiatric disease symptoms (e.g., dementia), attention deficits, oculomotor dysfunctions, altered non-discriminative aspects of pain experience of AD patients, and the disruption of their waking and sleeping patterns.

Spinocerebellar ataxia type 3 (SCA3): thalamic neurodegeneration occurs independently from thalamic ataxin-3 immunopositive neuronal intranuclear inclusions.

In the last years progress has been made regarding the involvement of the thalamus during the course of the currently known polyglutamine diseases. Although recent studies have shown that the thalamus consistently undergoes neurodegeneration in Huntington's disease (HD) and spinocerebellar ataxia type 2 (SCA2) it is still unclear whether it is also a consistent target of the pathological process of spinocerebellar ataxia type 3 (SCA3). Accordingly we studied the thalamic pathoanatomy and distribution pattern of ataxin-3 immunopositive neuronal intranuclear inclusions (NI) in nine clinically diagnosed and genetically confirmed SCA3 patients and carried out a detailed statistical analysis of our findings. During our pathoanatomical study we disclosed (i) a consistent degeneration of the ventral anterior, ventral lateral and reticular thalamic nuclei; (ii) a degeneration of the ventral posterior lateral nucleus and inferior and lateral subnuclei of the pulvinar in the majority of these SCA3 patients; and (iii) a degeneration of the ventral posterior medial and lateral posterior thalamic nuclei, the lateral geniculate body and some of the limbic thalamic nuclei in some of them. Upon immunocytochemical analysis we detected NI in all of the thalamic nuclei of all of our SCA3 patients. According to our statistical analysis (i) thalamic neurodegeneration and the occurrence of ataxin-3 immunopositive thalamic NI was not associated with the individual length of the CAG-repeats in the mutated SCA3 allele, the patients age at disease onset and the duration of SCA3 and (ii) thalamic neurodegeneration was not correlated with the occurrence of ataxin-3 immunopositive thalamic NI. This lack of correlation may suggest that ataxin-3 immunopositive NI are not immediately decisive for the fate of affected nerve cells but rather represent unspecific and pathognomonic morphological markers of SCA3.