Use a Saliva Test to ID Neurodegenerative 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 (Aβ42) and hyperphosphorylated tau in Alzheimer disease (AD) and the proteins α-synuclein (α-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 Aβ42 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 Aβ42 rather than tau. They detected a small but statistically significant increase in Aβ42 in patients with mild AD.¹

Similarly, salivary biomarkers might one day be used for PD diagnosis. The proteins α-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 α-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 α-Syn and increased DJ-1 in patients with PD versus controls. They also found a nonsignificant negative trend between α-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.

Key points:

• 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.

References:

References

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 α-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.