TNAP and P2X7R: New Plasma Biomarkers for Alzheimer’s Disease

Abstract

Over the last few years, intense research efforts have been made to anticipate or improve the diagnosis of Alzheimer’s disease by detecting blood biomarkers. However, the most promising blood biomarkers identified to date have some limitations, most of them related to the techniques required for their detection. Hence, new blood biomarkers should be identified to improve the diagnosis of AD, better discriminate between AD and mild cognitive impairment (MCI) and identify cognitively unimpaired (CU) older individuals at risk for progression to AD. Our previous studies demonstrated that both the purinergic receptor P2X7 and the tissue-nonspecific alkaline phosphatase ectoenzyme (TNAP) are upregulated in the brains of AD patients. Since both proteins are also present in plasma, we investigated whether plasma P2X7R and TNAP are altered in MCI and AD patients and, if so, their potential role as AD biomarkers. We found that AD but not MCI patients present increased plasma P2X7R levels. Nevertheless, TNAP plasma activity was increased in MCI patients and decreased in the AD group. ROC curve analysis indicated that measuring both parameters has a reasonable discriminating capability to diagnose MCI and AD conditions. In addition to confirming that individuals progressing to MCI have increased TNAP activity in plasma, longitudinal studies also revealed that CU individuals have lower plasma TNAP activity than stable controls. Thus, we propose that P2X7 and TNAP could serve as new plasma biomarkers for MCI and AD.

Hippocampal purinergic P2X7 receptor level is increased in Alzheimer’s disease patients, and associated with amyloid and tau pathologies

“…An earlier autoradiography study using P2X7R tracer [ 11 C]SMW139 showed comparable P2X7R levels in temporal cortex tissue from AD patients and nondemented controls (NCs) (29). A recent study showed a significant increase in plasma P2X7R levels in AD patients compared to those in control individuals (sensitivity 90.0%, specificity 50.22%) or patients with mild cognitive impairment (1). We found that the number of GFAP+ astrocytes and iba1+ microglia was not increased in the CA1, CA3 region of the hippocampus despite the increase in the level of P2X7R.…”