Immunoproteasome and LMP2 polymorphism in aged and Alzheimer's disease brains.
In this study, we investigated the presence and role of immunoproteasome and its LMP2 subunit polymorphism at codon 60 in Alzheimer's disease (AD). Immunoproteasome was present in brain areas such as hippocampus and cerebellum and localized in neurons, astrocytes and endothelial cells. A higher expression of immunoproteasome was found in brain of AD patients than in brain of non-demented elderly, being its expression in young brain negligible or absent. Furthermore, AD affected regions showed a partial decrease in proteasome trypsin-like activity. The study of LMP2 polymorphism (R/H) showed that it does not influence LMP2 expression (neither the mRNA nor mature protein) in brain tissue. However, control brain areas of AD patients carrying the RR genotype showed an increased proteasome activity in comparison with RH carriers. To test whether this effect of the genotype might be related to AD onset we performed a genetic study, which allowed us to exclude an association of LMP2 codon 60 polymorphism with AD onset, despite its influence on the proteasome activity in human brain.
Mishto
Michele
M
Department of Experimental Pathology, University of Bologna, 40126 Bologna, Italy. michele.mishto@unibo.it
Bellavista
Elena
E
Santoro
Aurelia
A
Stolzing
Alexandra
A
Ligorio
Claudia
C
Nacmias
Benedetta
B
Spazzafumo
Liana
L
Chiappelli
Martina
M
Licastro
Federico
F
Sorbi
Sandro
S
Pession
Annalisa
A
Ohm
Thomas
T
Grune
Tilman
T
Franceschi
Claudio
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D002102:Cadaver; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex