Caspase-6 Activation in Familial Alzheimer Disease Brains Carrying Amyloid Precursor Protein, Presenilin I or Presenilin II Mutations

• Published in: Journal of Neuropathology & Experimental Neurology
• Main Authors: Albrecht, Steffen, Bogdanovic, Nenad, Ghetti, Bernardino, Winblad, Bengt, LeBlanc, Andréa C.
• Format: Text
• Language: English
• Published: 2009
• Subjects: Article; Arctic
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079356; http://www.ncbi.nlm.nih.gov/pubmed/19915487; https://doi.org/10.1097/NEN.0b013e3181c1da10

We previously demonstrated the activation of Caspase-6 in the hippocampus and cortex in cases of mild, moderate, severe and very severe Alzheimer disease (AD). To determine whether Caspase-6 is also activated in familial AD, we performed an immunohistochemical analysis of active Caspase-6 and Tau cleaved by Caspase-6 in temporal cortex and hippocampal tissue sections from cases of familial AD. The cases included 5 carrying the amyloid precursor protein K670N, M671L Swedish mutation, 1 carrying the amyloid precursor protein E693G Arctic mutation, 2 each carrying the Presenilin I M146V, F105L, A431E, V261F, Y115C mutations, and 1 with the Presenilin II N141I mutation. Active Caspase-6 immunoreactivity was found in all cases. Caspase-6 immunoreactivity was observed in neuritic plaques or cotton wool plaques in some cases, neuropil threads and neurofibrillary tangles. These results indicate that Caspase-6 is activated in familial forms of AD, as previously observed in sporadic forms. Since sporadic and familial AD cases have similar pathological features, these results support a fundamental role of Caspase-6 in the pathophysiology of both familial and sporadic AD.