期刊
JOURNAL OF NEURAL TRANSMISSION
卷 115, 期 8, 页码 1165-1172出版社
SPRINGER WIEN
DOI: 10.1007/s00702-008-0067-y
关键词
Alzheimer's disease; uridine nucleotide; purinergic P2Y receptors; amyloid plaque; neurofibrillary tangle; neocortex
资金
- Wellcome Trust, UK
- National Medical Research Council [NMRC/0932/2005]
The uridine nucleotide-activated P2Y(2), P2Y(4) and P2Y(6) receptors are widely expressed in the brain and are involved in many CNS processes, including those which malfunction in Alzheimer's disease (AD). However, the status of these receptors in the AD neocortex, as well as their putative roles in the pathogenesis of neuritic plaques and neurofibrillary tangles, remain unclear. In this study, we used immunoblotting to measure P2Y(2), P2Y(4) and P2Y(6) receptors in two regions of the postmortem neocortex of neuropathologically assessed AD patients and aged controls. P2Y(2) immunoreactivity was found to be selectively reduced in the AD parietal cortex, while P2Y(4) and P2Y(6) levels were unchanged. In contrast, all three receptors were preserved in the occipital cortex, which is known to be minimally affected by AD neuropathology. Furthermore, reductions in parietal P2Y(2) immunoreactivity correlated both with neuropathologic scores and markers of synapse loss. These results provide a basis for considering P2Y(2) receptor changes as a neurochemical substrate of AD, and point towards uridine nucleotide-activated P2Y receptors as novel targets for disease-modifying AD pharmacotherapeutic strategies.
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