| Autor: |
Lippa, Carol F., Fujiwara, Hideo, Mann, David M.A., Giasson, Benoit, Baba, Minami, Schmidt, Marie L., Nee, Linda E., O'Connell, Brendan, Pollen, Dan A., St. George-Hyslop, Peter, Ghetti, Bernardino, Nochlin, David, Bird, Thomas D., Cairns, Nigel J., Lee, Virginia M.-Y., Iwatsubo, Takeshi, Trojanowski, John Q. |
| Zdroj: |
American Journal of Pathology; November 1998, Vol. 153 Issue: 5 p1365-1370, 6p |
| Abstrakt: |
Missense mutations in the α-synuclein gene cause familial Parkinson's disease (PD), and α-synuclein is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer's disease (AD). To determine whether α-synuclein is a component of LBs in familial AD (FAD) patients with known mutations in presenilin (n= 65) or amyloid precursor protein (n= 9) genes, studies were conducted with antibodies to α-, β-, and γ-synuclein. LBs were detected with α- but not β- or γ-synuclein antibodies in 22% of FAD brains, and α-synuclein-positive LBs were most numerous in amygdala where some LBs co-localized with tau-positive neurofibrillary tangles. As 12 (63%) of 19 FAD amygdala samples contained α-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, α-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of α-synuclein was reduced compared with control brains. The presence of α-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble α-synuclein aggregates into filaments that form LBs in many FAD patients, and we speculate that these inclusions may compromise the function and/or viability of affected neurons in the FAD brain. |
| Databáze: |
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