Hallervorden-Spatz syndrome (HSS) is a rare autosomal recessive disorder 
clinically characterized by extrapyramidal signs and progressive dementia. In a 
typical case, the clinical symptoms become apparent during late childhood, and 
usually the course is protracted over a decade or more. We recently had an 
opportunity to study the brains of two cases of HSS with a clinical course of 
over 30 years. Case 1 was a 44-year-old female and case 2 was a 37-year-old 
male. Grossly, the brains showed severe fronto-temporal lobar atrophy with 
abundant spheroids and mild iron deposits in the globus pallidus, associated 
with features of motor neuron disease. In addition, there was diffuse sponginess 
in the atrophic cortex as well as widespread Alzheimer's neurofibrillary tangles 
(NFTs) and Lewy bodies (LBs) in the cortical and subcortical regions, including 
the spinal cord. Ultrastructurally, NFTs were composed of paired helical 
filaments, and LBs of central dense cores with radiating fibrils. Discrete 
immunostaining was demonstrated in NFTs and neuropil threads with various 
antibodies against phosphorylated tau, and in LBs with antibody against 
alpha-synuclein. In addition, diffuse, overlapping immunoreactivity of 
alpha-synuclein and phosphorylated tau was seen within the cytoplasm of many 
neurons. However, when LBs and NFTs coexisted within the same neurons, they were 
clearly segregated. The findings of our present cases as well as those reported 
in the literature may indicate that simultaneous and extensive occurrence of 
abnormal phosphorylation of tau and accumulation of alpha-synuclein may 
constitute cardinal pathological features of HSS with protracted clinical 
course.