Caspase-6 activation in familial alzheimer disease brains carrying amyloid precursor protein or presenilin i or presenilin II mutations.
We previously demonstrated the activation of caspase-6 (Casp-6) in the hippocampus and cortex in cases of mild, moderate, severe, and very severe Alzheimer disease (AD). To determine whether Casp-6 is also activated in familial AD, we performed an immunohistochemical analysis of active Casp-6 and Tau cleaved by Casp-6 in temporal cortex and hippocampal tissue sections from cases of familial AD. The cases included 5 carrying the amyloid precursor protein K670N and M671L Swedish mutation, 1 carrying the amyloid precursor protein E693G Arctic mutation, 2 each carrying the Presenilin I M146V, F105L, A431E, V261F, and Y115C mutations, and 1 with the Presenilin II N141I mutation. Active Casp-6 immunoreactivity was found in all cases. Caspase-6 immunoreactivity was observed in neuritic plaques or in some cases cotton-wool plaques, and in neuropil threads and neurofibrillary tangles. These results indicate that Casp-6 is activated in familial forms of AD, as previously observed in sporadic forms. Because sporadic and familial AD cases have similar pathological features, these results support a fundamental role of Casp-6 in the pathophysiology of both familial and sporadic AD.
Albrecht
Steffen
S
Department of Pathology, McGill University, Montréal Children's Hospital, Montréal, Quebec, Canada.
Bogdanovic
Nenad
N
Ghetti
Bernardino
B
Winblad
Bengt
B
LeBlanc
Andréa C
AC
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D053178:Caspase 6 / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D019600:Neuropil Threads / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; D053766:Presenilin-2; D053178:Caspase 6