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(American Journal of Pathology. 2002;160:1725-1731.)
© 2002 American Society for Investigative Pathology

Regular Articles

Tau and -Synuclein Pathology in Amygdala of Parkinsonism-Dementia Complex Patients of Guam

Mark S. Forman^*, M. Luise Schmidt^*, Sanjay Kasturi^*, Daniel P. Perl, Virginia M.-Y. Lee^* and John Q. Trojanowski^*

From the Center for Neurodegenerative Disease Research and Department of Pathology and Laboratory Medicine,^*University of Pennsylvania, Philadelphia, Pennsylvania; and the Departments of Pathology and Psychiatry,Mt. Sinai School of Medicine, New York, New York

Amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder of Chamorro residents of Guam and the Mariana Islands, characterized by abundant neuron loss and tau neurofibrillary pathology similar to that observed in Alzheimer’s disease (AD). A variety of neurodegenerative diseases with tau pathology including ALS/PDC also have -synuclein positive pathology, primarily in the amygdala. We further characterized the tau and -synuclein pathology in the amygdala of a large series of 30 Chamorros using immunohistochemical and biochemical techniques. Tau pathology was readily detected in both affected and unaffected Chamorros. In contrast, -synuclein pathology was detected in 37% of patients with PDC but not detected in Chamorros without PDC or AD. The -synuclein aggregates often co-localized within neurons harboring neurofibrillary tangles suggesting a possible interaction between the two proteins. Tau and -synuclein pathology within the amygdala is biochemically similar to that observed in AD and synucleinopathies, respectively. Thus, the amygdala may be selectively vulnerable to developing both tau and -synuclein pathology or tau pathology may predispose it to synuclein aggregation. Furthermore, in PDC, tau and -synuclein pathology occurs independent of ß-amyloid deposition in amygdala thereby implicating the aggregation of these molecules in the severe neurodegeneration frequently observed in this location.

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