Caspase-6 activation in familial alzheimer disease brains carrying amyloid precursor protein or presenilin i or presenilin II mutations.

Abstract

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.

• Authors: Steffen Albrecht, Nenad Bogdanovic, Bernardino Ghetti, Bengt Winblad, Andréa C LeBlanc
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 68 Issue 12 Pg. 1282-93 (Dec 2009) ISSN: 1554-6578 [Electronic] England
• PMID: 19915487 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Protein Precursor
• Presenilin-1
• Presenilin-2
• Caspase 6

Topics

• Adult
• Aged
• Alzheimer Disease (enzymology, genetics, pathology)
• Amyloid beta-Protein Precursor (genetics)
• Brain (enzymology, pathology)
• Caspase 6 (metabolism)
• Enzyme Activation (physiology)
• Humans
• Immunohistochemistry
• Middle Aged
• Mutation
• Neurofibrillary Tangles (metabolism, pathology)
• Neuropil Threads (metabolism, pathology)
• Plaque, Amyloid (metabolism, pathology)
• Presenilin-1 (genetics)
• Presenilin-2 (genetics)