Why ask patients to “spit in a cup”? Statistically significant protein differences have been found in Alzheimer disease saliva, and trends have been observed for Parkinson disease.
Neurologists may find themselves asking patients to “spit in a cup.” Why?
Several studies suggest that saliva proteins contain biomarkers for neurodegenerative diseases.1-5 Researchers found pathological brain proteins in human saliva, including amyloid beta 1-42 (AÎ²42) and hyperphosphorylated tau in Alzheimer disease (AD) and the proteins Î±-synuclein (Î±-Syn) and DJ-1 in Parkinson disease (PD).1,2,5
Current AD guidelines recommend measuring increased phosphorylated tau and total tau levels and reduced AÎ²42 in cerebrospinal fluid.6-8 But getting cerebrospinal fluid requires a spinal tap. Not all patients are willing to do this, so researchers are studying other human fluids.
Shi and coworkers5 of the Department of Pathology, University of Washington School of Medicine, Seattle, found that the phosphorylated tau/tau ratio in saliva increases significantly in patients with AD compared with healthy controls. In their study, they stated, “Given the preliminary discovery that p-tau/t-tau levels are increased in AD, salivary p-tau and/or the p-tau/t-tau ratio could be excellent AD diagnostic markers.”
A different group working at the Hospital 12 de Octubre, in Madrid, Spain, focused mainly on the presence and concentration of AÎ²42 rather than tau. They detected a small but statistically significant increase in AÎ²42 in patients with mild AD.1
Similarly, salivary biomarkers might one day be used for PD diagnosis. The proteins Î±-Syn, along with DJ-1, decrease in PD cerebrospinal fluids,9 but, as mentioned, a spinal tap is not always practical.
The researchers in Washington again analyzed saliva to search for levels of Î±-Syn and DJ-1.2 The study included 24 patients who had PD compared with 25 age-matched control subjects who did not. The researchers could not find differences that reached statistical significance. They did, however, measure a clear trend for decreased Î±-Syn and increased DJ-1 in patients with PD versus controls. They also found a nonsignificant negative trend between Î±-Syn levels and Unified Parkinson’s Disease Rating Scale motor scores but no such trend for DJ-1.
Larger-scale studies are needed to confirm whether clinicians might use saliva to make a diagnosis of AD or PD.
• Saliva contains proteins found in neurodegenerative diseases.
• Statistically significant protein differences have been found in AD saliva, and trends have been observed for PD.
• Large-scale studies are needed to confirm whether saliva could be used in a clinical test for neurodegenerative disease.
1. Bermejo-Pareja F, Antequera D, Vargas T, et al. Saliva levels of Abeta1-42 as potential biomarker of Alzheimer’s disease: a pilot study. BMC Neurol. 2010;10:108.
2. Devic I, Hwang H, Edgar JS, et al. Salivary Î±-synuclein and DJ-1: potential biomarkers for Parkinson’s disease. Brain. 2011;134(Pt 7):e178.
3. Nam JW, Chung JW, Kho HS, et al. Nerve growth factor concentration in human saliva. Oral Dis. 2007;13:187-192.
4. Oh YS, Turner RJ. Effect of gamma-secretase inhibitors on muscarinic receptor-mediated calcium signaling in human salivary epithelial cells. Am J Physiol Cell Physiol. 2006;291:C76-C82.
5. Shi M, Sui YT, Peskind ER, et al. Salivary tau species are potential biomarkers of Alzheimer’s disease. J Alzheimers Dis. 2011;27:299-305.
6. Blennow KH, Hampel H. CSF markers for incipient Alzheimer’s disease. Lancet Neurol. 2003;2:605-613.
7. Dubois B, Feldman HH, Jacova C, et al. Revising the definition of Alzheimer’s disease: a new lexicon. Lancet Neurol. 2010;9:1118-1127.
8. Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6:734-746.
9. Hong Z, Shi M, Chung KA, et al. DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease. Brain. 2010;133(Pt 3):713-726.