Neuronal apoptosis inhibitory protein (NAIP)-like immunoreactivity in brains of adult patients with Down syndrome

In Down syndrome (DS), enhanced apoptosis (programmed cell death) may play a role in the pathogenesis of characteristic early mental retardation and p recocious neurodegeneration of Alzheimer-type. The human IAP (inhibitor of apoptosis proteins) genes (NAIP, c-IAP-2/HIAP-1 , c-IAP-1/Hiap-2, XIAP, survivin) are an evolutionary conserved family of p roteins which prevent cell death across species, implying that they act at a central, highly conserved point in the cell death cascade. Evidence for d ownregulation of NAIP-mRNA in fetal DS (23rd week of gestation), as found b y subtractive hybridization technique challenged studies at the protein lev el in adult DS brain specimen. NAIP-like immunoreactivity was determined in four different regions of cere bral cortex and cerebellum in 9 adult DS patients with Alzheimer-like neuro pathologic lesions, 9 Alzheimer disease (AD) patients as compared to 9 cont rols. For the first time, NAIP-IR could be demonstrated in different cortic al regions of the human brain. Compared to control subjects, western blotti ng demonstrated significantly decreased levels in parietal and occipital co rtex in DS and in frontal and occipital cortex in AD. While the mode of NAI P action is unknown, inhibition of certain caspases has already been demons trated for other IAP-family members (c-IAP1, c-IAP2 and XIAP). Although dec reased NAIP-IR of certain brain regions in DS and AD awaits further confirm ation, the results suggest that alterations of apoptosis regulatory (inhibi tory) proteins may be another feature of neurodegeneration in DS and AD.