Tau and alpha-synuclein pathology in amygdala of Parkinsonism-dementia complex patients of Guam.
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 alpha-synuclein positive pathology, primarily in the amygdala. We further characterized the tau and alpha-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, alpha-synuclein pathology was detected in 37% of patients with PDC but not detected in Chamorros without PDC or AD. The alpha-synuclein aggregates often co-localized within neurons harboring neurofibrillary tangles suggesting a possible interaction between the two proteins. Tau and alpha-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 alpha-synuclein pathology or tau pathology may predispose it to synuclein aggregation. Furthermore, in PDC, tau and alpha-synuclein pathology occurs independent of beta-amyloid deposition in amygdala thereby implicating the aggregation of these molecules in the severe neurodegeneration frequently observed in this location.
Forman
Mark S
MS
Center for Neurodegenerative Disease Research and Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Schmidt
M Luise
ML
Kasturi
Sanjay
S
Perl
Daniel P
DP
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
D000368:Aged; D000369:Aged, 80 and over; D000679:Amygdala / Q000737:chemistry / Q000473:pathology*; D015153:Blotting, Western; D003704:Dementia / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006141:Guam; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology*; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins / Q000378:metabolism*
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins