Immunohistochemical evidence of P2X7R, P2X4R and CaMKK2 in pyramidal neurons of frontal cortex does not align with Alzheimer's disease

Jessica Gaff; Connie Jackaman; John Papadimitriou; Shelley Waters; Catriona McLean; Patricia Price

doi:10.1016/j.yexmp.2021.104636

Immunohistochemical evidence of P2X7R, P2X4R and CaMKK2 in pyramidal neurons of frontal cortex does not align with Alzheimer's disease

Exp Mol Pathol. 2021 Jun:120:104636. doi: 10.1016/j.yexmp.2021.104636. Epub 2021 Apr 7.

Authors

Jessica Gaff¹, Connie Jackaman², John Papadimitriou³, Shelley Waters¹, Catriona McLean⁴, Patricia Price⁵

Affiliations

¹ School of Pharmacy and Biomedical Science, Curtin University, Australia.
² School of Pharmacy and Biomedical Science, Curtin University, Australia; Curtin Health Innovation Research Institute, Curtin University, Australia.
³ Pathology & Laboratory Medicine, University of Western Australia, Australia; Pathwest Laboratories, Western Australia, Australia.
⁴ Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Victoria, Australia; Victorian Brain Bank, Florey Institute of Neuroscience and Mental Health, Victoria, Australia.
⁵ School of Pharmacy and Biomedical Science, Curtin University, Australia; Curtin Health Innovation Research Institute, Curtin University, Australia. Electronic address: patricia.price@curtin.edu.au.

PMID: 33838119
DOI: 10.1016/j.yexmp.2021.104636

Abstract

Alzheimer's disease (AD) is an incurable neurodegenerative condition resulting in progressive cognitive decline. Pathological features include Aβ plaques, neurofibrillary tangles, neuroinflammation and neuronal death. Purinergic receptors 7 and 4 (P2X7R and P2X4R) and calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) are implicated in neuronal death. We used immunohistochemistry to investigate the distribution of these proteins in neurones from frontal cortex of donors (n = 3/group; aged 79-83 years) who died with and without AD. Neurones were identified morphologically and immunoperoxidase staining was achieved using commercial antibodies. Immunoreactive neurones were counted for each protein by 2-3 raters blinded to the diagnoses. We observed no differences in percentages of P2X7R, P2X4R or CaMKK2 positive neurones (p = 0.2-0.99), but sections from individuals with AD had marginally fewer neurones (p = 0.10). Hence P2X7R, P2X4R or CaMKK2 appear to be expressed in neurones from older donors, but expression does not associate with AD.

Keywords: Alzheimer's disease; CaMKK2; Neurones; P2X4R; P2X7R.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / metabolism
Alzheimer Disease / pathology*
Biomarkers / metabolism*
Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism*
Case-Control Studies
Female
Frontal Lobe / metabolism
Frontal Lobe / pathology*
Humans
Immunohistochemistry
Male
Prognosis
Pyramidal Cells / metabolism
Pyramidal Cells / pathology*
Receptors, Purinergic P2X4 / metabolism*
Receptors, Purinergic P2X7 / metabolism*

Substances

Biomarkers
P2RX4 protein, human
P2RX7 protein, human
Receptors, Purinergic P2X4
Receptors, Purinergic P2X7
CAMKK2 protein, human
Calcium-Calmodulin-Dependent Protein Kinase Kinase