AMYOTROPHIC-LATERAL-SCLEROSIS PARKINSONISM-DEMENTIA COMPLEX OF GUAM -QUANTITATIVE NEUROPATHOLOGY, IMMUNOHISTOCHEMICAL ANALYSIS OF NEURONALVULNERABILITY, AND COMPARISON WITH RELATED NEURODEGENERATIVE DISORDERS

Amyotrophic lateral sclerosis/parkinsonism-dementia complex (lytico-bo dig) is a chronic neurodegenerative disorder with high prevalence amon g the native Chamorro population of Guam. Neuropathological, biochemic al, and immunohistochemical analyses were performed on a relatively la rge series of Guamanian cases and compared to Alzheimer's disease case s. Thioflavin S and antibodies to amyloid beta A4 and tau proteins wer e used for analysis of pathological changes, and antibodies to the cal cium-binding proteins parvalbumin and calretinin, and to a nonphosphor ylated epitope on neurofilament protein to study select neuronal popul ations. A differential distribution of neurofibrillary tangles was obs erved in the neocortex of Guamanian cases compared to Alzheimer's dise ase cases, with much higher lesion counts in supragranular than in inf ragranular layers. Also, Guamanian cases with predominant parkinsonism had generally higher neurofibrillary tangle densities than cases with predominant amyotrophic lateral sclerosis. In addition, there was a c ertain degree of heterogeneity, qualitatively and quantitatively, in t he biochemical distribution of tau proteins among Guamanian and Alzhei mer's disease cases as revealed by Western blot analysis. Previous stu dies have suggested that the clinical symptomatology observed in patie nts suffering from Alzheimer's disease is related to the dramatic loss of specific corticocortically projecting neurons in the neocortex. In terestingly, a subset of neurofilament-rich pyramidal neurons known to be dramatically affected in Alzheimer's disease appears to be resista nt in lytico-bodig. Finally, as in Alzheimer's disease, calcium-bindin g protein-containing interneurons are not affected. These data suggest that the set of projection neurons affected in Guamanian cases may no t correspond to those involved in Alzheimer's disease, and that both d isorders are characterized by specific patterns of neuronal vulnerabil ity.