Differential regulation of inhibitors of apoptosis proteins in Alzheimer's disease brains.
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.
Christie
Lori-Ann
LA
Institute for Brain Aging and Dementia, 1113 Gillespie Neuroscience Research Facility, University of California, Irvine, CA 92697, USA. lori@uci.edu
Su
Joseph H
JH
Tu
Christina H
CH
Dick
Malcolm C
MC
Zhou
Jun
J
Cotman
Carl W
CW
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology; D001344:Autopsy; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D015415:Biomarkers; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D003704:Dementia / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D018613:Microscopy, Confocal; D016874:Neurofibrillary Tangles / Q000473:pathology; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000096:biosynthesis / Q000235:genetics; D058225:Plaque, Amyloid / Q000473:pathology; D011237:Predictive Value of Tests; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism
D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D051636:X-Linked Inhibitor of Apoptosis Protein; D016875:tau Proteins; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases