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01-08-2008 | Alzheimer's Disease and Related Disorders - Original Article

Selective loss of P2Y₂ nucleotide receptor immunoreactivity is associated with Alzheimer’s disease neuropathology

Authors: Mitchell K. P. Lai, Michelle G. K. Tan, Sara Kirvell, Carl Hobbs, Jasinda Lee, Margaret M. Esiri, Christopher P. Chen, Paul T. Francis

Published in: Journal of Neural Transmission | Issue 8/2008

Abstract

The uridine nucleotide-activated P2Y₂, P2Y₄ and P2Y₆ 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 P2Y₂, P2Y₄ and P2Y₆ receptors in two regions of the postmortem neocortex of neuropathologically assessed AD patients and aged controls. P2Y₂ immunoreactivity was found to be selectively reduced in the AD parietal cortex, while P2Y₄ and P2Y₆ 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 P2Y₂ immunoreactivity correlated both with neuropathologic scores and markers of synapse loss. These results provide a basis for considering P2Y₂ 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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Title: Selective loss of P2Y2 nucleotide receptor immunoreactivity is associated with Alzheimer’s disease neuropathology
Authors: Mitchell K. P. Lai
Michelle G. K. Tan
Sara Kirvell
Carl Hobbs
Jasinda Lee
Margaret M. Esiri
Christopher P. Chen
Paul T. Francis
Publication date: 01-08-2008
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 8/2008
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-008-0067-y

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Selective loss of P2Y₂ nucleotide receptor immunoreactivity is associated with Alzheimer’s disease neuropathology

Abstract

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