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

Steffen Albrecht, Nenad Bogdanovic, Bernardino Ghetti, Bengt Winblad, Andréa C. Leblanc

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1282-1293
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume68
Issue number12
DOIs
StatePublished - Dec 1 2009

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Keywords

  • Alzheimer disease
  • Arctic mutation
  • Casp-6
  • Familial Alzheimer disease
  • Presenilin I mutation
  • Sporadic Alzheimer disease
  • Swedish mutation
  • Tau cleaved by Casp-6

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

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