ArticleAnnals of neurology2026
Regional and Compartmental Changes Drive Progressive Patterns of Striatal Degeneration in X-Linked Dystonia Parkinsonism.
Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveInitially described in 1976, X-linked dystonia parkinsonism (XDP) is a neurodegenerative disease that can be characterized by the presentation of dystonia and parkinsonism symptoms. Although this disease bears some resemblance to other neurodegenerative diseases in terms of symptomatology, the pathological signature of XDP is still unclear, in part because of the limited research that has been conducted. This study aims to delineate in detail the neurochemical changes occurring in the post mortem human XDP striatum and to explore their relevance to clinical symptomatology.
methodsThe profiles of immunohistochemical expression of multiple spiny projection neurons and projection fiber markers was assessed in the post mortem tissue from the basal ganglia of 18 XDP and 10 neurologically normal cases.
resultsWe present evidence that degeneration of the XDP striatum follows a dorsoventral gradient, with greater vulnerability in the matrix compartment of the striatum. Considering the available clinical data of the cases investigated, we propose that this pattern of neurodegeneration is more closely associated with the duration of the disease than SINE-VNTR-Alu repeat length; however, repeat length is inversely correlated with XDP symptom onset and, therefore, influences the clinical timeline.
interpretationOur findings provide a novel perspective on the pattern and degree of degeneration of the XDP striatum. We propose that the matrix compartment is more vulnerable to disease impact relative to striosomes than initially thought, and the pattern of striatal degeneration may be indicative of the breakdown of a wider cortico-basal ganglia neural circuit over the duration of the disease. ANN NEUROL 2026;100:751-767.
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