THE CORTICAL NEURITIC PATHOLOGY OF HUNTINGTONS-DISEASE

We have studied the brains of 10 patients with clinically and patholog ically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nin e cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39 , 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolas e (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PG P 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of al l brains studied. No dystrophic neurites were found in subcortical are as or cerebellum. Sections from cortical areas 8 and 24 from the two b rains with the most and least ubiquitin-immunoreactive neurites were s tained with antibodies to beta-amyloid precursor protein, tau, glial f ibrillary acidic protein, neurofilament protein, alpha B crystallin, G ABA, cholecystokinin and somatostatin. The dystrophic neurites were fo und to also react with P-amyloid precursor protein. Electron microscop y showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100nm were interspersed betwe en randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not be en seen in control brain and differ from age-related neuritic degenera tion and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, a nd, ultrastructurally, the intraneuronal filamentous inclusions in mot or neuron disease. The areal density of these neurites was quantified in 20 microscopic fields in the superior frontal and anterior cingulat e sections (Brodmann areas 8 and 24) and did not correlate with the Vo nsattel grade, suggesting that they are an independent and possibly pr imary cortical pathology in Huntington's disease.