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Alzheimer’s disease has proven to be largely intractable to treatment, despite years of research, and numerous trials of therapies that target the hallmarks of the disease – amyloid plaques and neurofibrillary tangles. The etiology of Alzheimer’s disease remains elusive. There is a growing body of evidence for an infectious trigger of Alzheimer’s disease, and, in particular, the focus has been on the oral pathogen Porphyromonas gingivalis (P. gingivalis). Reports of the expression of a misfolded form of p53 in non-neuronal cells (fibroblasts, peripheral blood mononuclear cells, and B cells) and serum, which appears several years before clinical symptoms manifest, may provide further support for the role of bacteria in general, and P. gingivalis in particular, in the initiation of the disease. This review presents a model of the pathway from initial oral infection with P. gingivalis to amyloid plaque formation and neuronal degeneration, via the steps of chronic periodontitis; secretion of the inflammagens lipopolysaccharide and gingipains into the bloodstream; induction of an inflammatory response in both peripheral cells and tissues; disruption of the blood-brain barrier, and entry into the central nervous system of the inflammagens and the P. gingivalis bacteria themselves. In this model, the misfolded p53 (or “unfolded p53”; up53) is induced in non-neuronal cells and upregulated in serum as a result of oxidative stress due to lipopolysaccharide from P. gingivalis. up53 is therefore a potential biomarker for early diagnosis of the presence of a causative agent of Alzheimer’s disease. Fastidious dental hygiene and aggressive antibiotic treatment may prevent the patient progressing to clinical Alzheimer’s disease if serum up53 is detected at this pre-symptomatic stage.

Alzheimer's disease is one of the most common causes of dementia nowadays, and its prevalence increases over time. Because of this and the difficulty of its diagnosis, accurate methods for the analysis of specific biomarkers for an early diagnosis of this disease are much needed. Recently, the levels of unfolded isoform of the multifunctional protein p53 in plasma have been proved to increase selectively in Alzheimer's Disease patients in comparison with healthy subjects, thus entering the list of biomarkers that can be used for the diagnosis of this illness. We present here the development of an electrochemical immunosensor based on nanostructured screen-printed carbon electrodes for the quantification of unfolded p53 in plasma samples. The sensor shows a suitable linear range (from 2 to 50 nM) for its application in real blood samples and a very low limit of detection (0.05 nM). The concentration of unfolded p53 has been accurately detected in plasma of elderly people in healthy conditions, subjects with mild cognitive impairment (MCI) and Alzheimer's Disease (AD) subjects, obtaining results with no significant differences to those provided by an ELISA assay. These results support the possibility of measuring unfolded p53 levels with a cheap, simple and miniaturized device with a promising future for point-of-care applications in the early diagnosis of Alzheimer's dementia. Image 1 • An immunosensor for the detection of unfolded p53 protein, an emerging biomarker for Alzheimer's Disease, was developed. • A competitive immunoassay was carried out using screen-printed carbon electrodes nanostructured with gold nanoparticles. • A high selectivity is achieved using an antibody that only reacts with an epitope present in the unfolded p53 protein. • A wide dynamic range (2–50 nM) has been obtained with excellent analytical characteristics. • This biosensor was applied for unfolded p53 quantification in plasma samples with high accuracy. [ABSTRACT FROM AUTHOR]

Aims: There are several candidate biomarkers for AD and PD which differ in sensitivity, specificity, cost-effectiveness, invasiveness, logistical and technical demands. This study is aimed to test whether plasma concentration of unfolded p53 may help to discriminate among the neurodegenerative processes occurring in Mild Cognitive Impairment, Alzheimer's disease and Parkinson's disease., Methods: An electrochemical immunosensor was used to measure unfolded p53 in plasma samples of 20 Mild Cognitive Impairment (13 males/7 females; mean age 74.95±5.31), 20 Alzheimer's (11 males/9 females; mean age: 77.25±7.79), 15 Parkinson's disease patients (12 males/3 females; mean age: 68.60 ± 7.36) and its respective age/sex/studies-matched controls., Results: We observed a significantly higher concentration of unfolded p53 in the plasma of patients of each of the three pathologies with respect to their control groups (p=0.000). Furthermore, the plasma concentration of unfolded p53 was significantly higher in Alzheimer's disease patients in comparison with Mild Cognitive Impairment patients (p=0.000) and Parkinson's disease patients (p=0.006). No significant difference between Mild Cognitive Impairment and Parkinson's disease patients was observed (p=0.524)., Conclusion: Our results suggest that unfolded p53 concentration in the plasma may be a useful biomarker for an undergoing neuropathological process that may be common, albeit with different intensity, to different diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)