Tau-predominant-associated pathology in a sporadic late-onset Hallervorden-Spatz syndrome

Mov Disord. 2006 Jan;21(1):107-11. doi: 10.1002/mds.20661.

Abstract

Hallervorden-Spatz syndrome (HSS) is a heterogeneous clinicopathological disorder currently included within the broader title of neurodegeneration with brain iron accumulation (NBIA). The classic histological hallmarks of HSS are axonal spheroids and excessive iron-containing granules accompanied by neuronal loss and gliosis in the globus pallidus and substantia nigra reticulata. In the modern literature, attention has been drawn to the co-occurrence of two other histological markers: Lewy bodies mainly composed of abnormal alpha-synuclein, and neurofibrillary tangles due to hyperphosphorilated tau aggregation. Discrepancies exist regarding the importance of these molecular changes and its relevance for the nosology of HSS. Most authors have emphasized the importance of the Lewy body-like pathology, favoring the inclusion of HSS within the alpha-synucleinopathies. We report on a case of late-onset HSS, with the typical histological findings restricted to the basal ganglia and cerebellum in which tau pathology was exceedingly more abundant than alpha-synuclein pathology. This case contributes to the increasing evidence about the heterogeneity of HSS. We favor the view that the molecular changes and the protein misfolding underlying the Lewy body and tangle formation in HSS/NBIA are secondary to the main pathological process and should not be taken as the basis for its nosological classification.

Publication types

  • Case Reports

MeSH terms

  • Axons / pathology
  • Basal Ganglia / pathology
  • Brain / pathology*
  • Brain Stem / pathology
  • Diagnosis, Differential
  • Humans
  • Inclusion Bodies / pathology
  • Iron / analysis
  • Lewy Bodies / pathology
  • Male
  • Middle Aged
  • Myelin Sheath / pathology
  • Neurodegenerative Diseases / pathology
  • Neurofibrillary Tangles / pathology
  • Pantothenate Kinase-Associated Neurodegeneration / genetics
  • Pantothenate Kinase-Associated Neurodegeneration / pathology*
  • Protein Folding
  • Spheroids, Cellular / pathology
  • Tauopathies / genetics
  • Tauopathies / pathology*
  • Thalamic Nuclei / pathology
  • alpha-Synuclein / analysis
  • tau Proteins / analysis

Substances

  • alpha-Synuclein
  • tau Proteins
  • Iron