Caspase-6 activity predicts lower episodic memory ability in aged individuals

NEUROBIOLOGY OF AGING

卷:34

Article

Ramcharitar, Jasmine^1,2  Afonso, Veronica M.^1,2  Albrecht, Steffen³  Bennett, David A.^4,5  LeBlanc, Andrea C.^1,2 

[1] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada

[2] McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Bloomfield Ctr Res Aging, Montreal, PQ H3T 1E2, Canada

[3] McGill Univ, Dept Pathol, Montreal, PQ, Canada

[4] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

[5] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA

关键词: Caspase-6;    Alzheimer disease;    Memory performance;    Aged individuals and cognition;    Episodic memory;    Working memory;    Semantic memory;    Visuospatial abilities;    Perceptual speed;   

DOI  :  10.1016/j.neurobiolaging.2013.01.007

来源: Elsevier

【 摘 要 】

Caspase-6 (Casp6), a cysteinyl protease that induces axonal degeneration, is activated early in Alzheimer Disease (AD) brains. To determine whether Casp6 activation is responsible for early cognitive impairment, we investigated the abundance of Casp6 activity, paired helical filament-1 (PHF-1) phosphorylated Tau and amyloid beta peptide (A beta) pathology by immunohistochemistry in the hippocampal formation of aged non-cognitively impaired (NCI) individuals. Casp6 activity was restricted to the entorhinal cortex (ERC) and CA1 regions of the hippocampus. Pathology scores were then correlated with cognitive scores obtained within 1 year of death. Regression analyses revealed that ERC and CA1 Casp6 activity were the main contributor to lower episodic memory performance, whereas ERC PHF-1 pathology predicted lower semantic and working memory performance. A beta did not correlate with any of the cognitive tests. Because Casp6 activity and PHF-1 pathology are intimately associated with AD pathology and memory decline is an early event in AD, we conclude that Casp6 activity and PHF-1 immunoreactivity in ERC identifies aged individuals at risk for developing AD. (C) 2013 Elsevier Inc. All rights reserved.

【 授权许可】

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