Differential regulation of inhibitors of apoptosis proteins in Alzheimer’s disease brains

• Published in: Neurobiology of disease Vol. 26; no. 1; pp. 165 - 173
• Main Authors: Christie, Lori-Ann, Su, Joseph H, Tu, Christina H, Dick, Malcolm C, Zhou, Jun, Cotman, Carl W
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2007; Elsevier
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - psychology; Alzheimer’s disease; Autopsy; Baculoviral IAP Repeat-Containing 3 Protein; Biomarkers; Blotting, Western; Brain Chemistry - physiology; Caspase activation; cIAP-2; Dementia - metabolism; Dementia - pathology; Female; Gene Expression Regulation; Humans; Immunohistochemistry; Inhibitor of apoptosis; Inhibitor of Apoptosis Proteins - biosynthesis; Inhibitor of Apoptosis Proteins - genetics; Male; Microscopy, Confocal; MMSE; NAIP; Neurodegeneration; Neurofibrillary tangles; Neurofibrillary Tangles - pathology; Neurology; Neuronal Apoptosis-Inhibitory Protein - biosynthesis; Neuronal Apoptosis-Inhibitory Protein - genetics; Plaque, Amyloid - pathology; Predictive Value of Tests; Tau; tau Proteins - metabolism; Temporal Lobe - metabolism; Temporal Lobe - pathology; Ubiquitin-Protein Ligases; X-Linked Inhibitor of Apoptosis Protein - biosynthesis; X-Linked Inhibitor of Apoptosis Protein - genetics; XIAP; Caspase activation; Neurofibrillary tangles; Alzheimer’s disease; Neurodegeneration; MMSE; XIAP; cIAP-2; Tau; NAIP; Inhibitor of apoptosis
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2006.12.017

Abstract Neuronal degeneration linked to apoptosis can be inhibited by a family of proteins known as inhibitors of apoptosis proteins (IAPs). We examined three members of the IAP family that are implicated in the regulation of neuronal death. We assessed NAIP, XIAP, and cIAP-2 protein levels in the entorhinal cortex of non-demented, cognitively impaired and Alzheimer’s disease cases. Levels of paired helical filament-1 (PHF-1), a marker of neurofibrillary tangles, were assessed to determine their relationship to IAP levels. NAIP was decreased in AD cases compared to mildly impaired and unimpaired cases, and this decrease was associated with increased PHF-1 levels. Low NAIP levels were associated with higher Braak and Braak tangle stage and cognitive dysfunction. XIAP levels were higher in AD cases and cIAP-2 levels did not vary with clinical status. Our data suggest that decreased NAIP may place neurons at risk for the development of tangles and apoptosis.