Peripheral Biomarkers for Early Detection of Alzheimer’s and Parkinson’s Diseases

Abstract

Neurological disorders are found to be influencing the peripheral tissues outside CNS. Recent developments in biomarkers for CNS have emerged with various diagnostic and therapeutic shortcomings. The role of central biomarkers including CSF-based and molecular imaging-based probes are still unclear for early diagnosis of major neurological diseases. Current trends show that early detection of neurodegenerative diseases with non-invasive methods is a major focus of researchers, and the development of biomarkers aiming peripheral tissues is in demand. Alzheimer's and Parkinson's diseases are known for the progressive loss in neural structures or functions, including the neural death. Various dysfunctions of metabolic and biochemical pathways are associated with early occurrence of neuro-disorders in peripheral tissues including skin, blood cells, and eyes. This article reviews the peripheral biomarkers explored for early detection of Alzheimer's and Parkinson's diseases including blood cells, skin fibroblast, proteomics, saliva, olfactory, stomach and colon, heart and peripheral nervous system, and others. Graphical Abstract ᅟ.

α-Synuclein heteromers with ß-amyloid and tau decreased in red blood cells of Alzheimer’s disease and Lewy Body dementia patients.

“…Very few data are available on the blood levels of amyloid protein. Previous cross-sectional studies con rmed that plasma Aβ of AD patients is not much different from normal controls [55], but somewhat promising results have been seen for combinations of Aβ 1−42 and Aβ 1−40 . Of note, recent studies allowed us to measure very low amounts of several Aβ-related peptides in plasma using ultrasensitive assays, supporting the use of plasma Aβ42/40 ratios as surrogate biomarkers of cerebral Aβ deposition [56,57].…”

Development of early diagnosis of Parkinson's disease: Illusion or reality?

“…15 It becomes toxic as a result of intraneuronal accumulation due to an impaired proteasomal degradation by ubiquitin-C-terminal hydrolase-L1 and β-glucocerebrosidase, 25,38,39 followed by aggregation, misfolding, and phosphorylation at serine-129. 40 Although toxic α-synuclein affects all neurons, it appears to provide a semi-specific effect on nigrostriatal dopaminergic neurons, probably enhancing the cytosolic dopamine autotoxicity. 11,41 Tau proteinopathy, like α-synucleinopathy, promotes neurodegeneration due to impaired axonal transport in affected neurons, including nigrostriatal dopaminergic neurons.…”

“…It was shown that the concentration of total α-synuclein decreased in CSF and plasma in PD patients, whereas the concentrations of toxic phosphorylated at serine-129 and oligomeric α-synuclein increased in both BF compared to age-matched control. 19,40,[75][76][77][78] The sensitivity and specificity of the PD diagnosis increase up to 89.3% and 90.6%, when assessing the ratio of α-synuclein oligomers to the total content of α-synuclein. 13,21,75 Aggregated and phosphorylated tau protein is also considered as a biomarker, since their concentrations decrease in CSF in PD patients.…”

“…In addition to CSF and plasma, PD biomarkers were found in saliva and urine. 40,[96][97][98] It should be emphasized that, although the individual biomarkers found so far in PD patients are not specific, the accuracy of ED can be increased by using a combination of various diagnostic biomarkers. 13,21,72,80 In addition to plasma biomarkers, blood biomarkers of PD include changes in the expression of specific genes and phenotype of blood cells due to changes in the environment (plasma).…”

Evaluation of salivary acetylcholinesterase and pseudocholinesterase in patients with Alzheimer's disease: A case–control study

“…Many studies about salivary biomarkers in patients with AD have been conducted; but to the best of our knowledge, few studies have been performed on salivary cholinesterase enzyme changes and the benefits of saliva in AD. Therefore, the aim of this study is to compare salivary AChE and PChE in patients with AD and in healthy control groups.…”