Salivary Biomarkers for Alzheimer's Disease and Related Disorders

Overview

Journal Neurol Ther

Publisher Springer

Specialty Neurology

Date 2019 Dec 14

PMID 31833026

Citations 38

Authors

Nicholas J Ashton

Mark Ide

Henrik Zetterberg

Kaj Blennow

Affiliations

Soon will be listed here.

Abstract

The search for accessible and cost-effective biomarkers to complement current cerebrospinal fluid (CSF) and imaging biomarkers in the accurate detection of Alzheimer disease (AD) and other common neurodegenerative disorders remains a challenging task. The advances in ultra-sensitive detection methods has highlighted blood biomarkers (e.g. amyloid-β and neurofilament light) as a valuable and realistic tool in a diagnostic or screening process. Saliva, however, is also a rich source of potential biomarkers for disease detection and offers several practical advantages over biofluids that are currently examined for neurodegenerative disorders. However, while this may be true for the general population, challenges in collecting saliva from an elderly population should be seriously considered. In this review, we begin by discussing how saliva is produced and how age-related conditions can modify saliva production and composition. We then focus on the data available which support the concept of salivary amyloid-β, tau species and novel biomarkers in detecting AD and alpha-synuclein (α-syn) in Parkinson's disease (PD).

Citing Articles

Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases.

Liu Z, Song S Genes (Basel). 2025; 16(2).

PMID: 40004464 PMC: 11855287. DOI: 10.3390/genes16020135.

Guidelines for the standardization of pre-analytical variables for salivary biomarker studies in Alzheimer's disease research: An updated review and consensus of the Salivary Biomarkers for Dementia Research Working Group.

Ng T, Udeh-Momoh C, Lim M, Gleerup H, Leifert W, Ajalo C Alzheimers Dement. 2024; 21(2):e14420.

PMID: 39737743 PMC: 11848381. DOI: 10.1002/alz.14420.

Alzheimer's disease: a review on the current trends of the effective diagnosis and therapeutics.

Abdul Manap A, Almadodi R, Sultana S, Sebastian M, Kavani K, Lyenouq V Front Aging Neurosci. 2024; 16:1429211.

PMID: 39185459 PMC: 11341404. DOI: 10.3389/fnagi.2024.1429211.

Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.

Zhang J, Zhang Y, Wang J, Xia Y, Zhang J, Chen L Signal Transduct Target Ther. 2024; 9(1):211.

PMID: 39174535 PMC: 11344989. DOI: 10.1038/s41392-024-01911-3.

Role of 14-3-3 protein family in the pathobiology of EBV in immortalized B cells and Alzheimer's disease.

Awasthi P, Kumar D, Hasan S Front Mol Biosci. 2024; 11:1353828.

PMID: 39144488 PMC: 11322100. DOI: 10.3389/fmolb.2024.1353828.

References

Dodds M, Johnson D, Yeh C . Health benefits of saliva: a review. J Dent. 2005; 33(3):223-33. DOI: 10.1016/j.jdent.2004.10.009. View

Gupta A, Epstein J, Sroussi H . Hyposalivation in elderly patients. J Can Dent Assoc. 2006; 72(9):841-6. View

Jasim H, Olausson P, Hedenberg-Magnusson B, Ernberg M, Ghafouri B . The proteomic profile of whole and glandular saliva in healthy pain-free subjects. Sci Rep. 2016; 6:39073. PMC: 5157045. DOI: 10.1038/srep39073. View

Mielke M, Hagen C, Xu J, Chai X, Vemuri P, Lowe V . Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography. Alzheimers Dement. 2018; 14(8):989-997. PMC: 6097897. DOI: 10.1016/j.jalz.2018.02.013. View

Sayer R, Law E, Connelly P, Breen K . Association of a salivary acetylcholinesterase with Alzheimer's disease and response to cholinesterase inhibitors. Clin Biochem. 2004; 37(2):98-104. DOI: 10.1016/j.clinbiochem.2003.10.007. View

Mattsson N, Zetterberg H, Janelidze S, Insel P, Andreasson U, Stomrud E . Plasma tau in Alzheimer disease. Neurology. 2016; 87(17):1827-1835. PMC: 5089525. DOI: 10.1212/WNL.0000000000003246. View

Percival R, Challacombe S, Marsh P . Flow rates of resting whole and stimulated parotid saliva in relation to age and gender. J Dent Res. 1994; 73(8):1416-20. DOI: 10.1177/00220345940730080401. View

Carro E, Bartolome F, Bermejo-Pareja F, Villarejo-Galende A, Molina J, Ortiz P . Early diagnosis of mild cognitive impairment and Alzheimer's disease based on salivary lactoferrin. Alzheimers Dement (Amst). 2017; 8:131-138. PMC: 5470603. DOI: 10.1016/j.dadm.2017.04.002. View

Jack Jr C, Bennett D, Blennow K, Carrillo M, Dunn B, Budd Haeberlein S . NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14(4):535-562. PMC: 5958625. DOI: 10.1016/j.jalz.2018.02.018. View

10.

Boros I, KESZLER P, Zelles T . Study of saliva secretion and the salivary fluoride concentration of the human minor labial glands by a new method. Arch Oral Biol. 1999; 44 Suppl 1:S59-62. DOI: 10.1016/s0003-9969(99)90022-5. View

11.

Ashton N, Leuzy A, Lim Y, Troakes C, Hortobagyi T, Hoglund K . Increased plasma neurofilament light chain concentration correlates with severity of post-mortem neurofibrillary tangle pathology and neurodegeneration. Acta Neuropathol Commun. 2019; 7(1):5. PMC: 6327431. DOI: 10.1186/s40478-018-0649-3. View

12.

Zhang Y, Sun J, Lin C, Abemayor E, Wang M, Wong D . The emerging landscape of salivary diagnostics. Periodontol 2000. 2015; 70(1):38-52. DOI: 10.1111/prd.12099. View

13.

Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E, Bjerke M . CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis. Lancet Neurol. 2016; 15(7):673-684. DOI: 10.1016/S1474-4422(16)00070-3. View

14.

Vergallo A, Megret L, Lista S, Cavedo E, Zetterberg H, Blennow K . Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease. Alzheimers Dement. 2019; 15(6):764-775. DOI: 10.1016/j.jalz.2019.03.009. View

15.

Beach T, Adler C, Serrano G, Sue L, Walker D, Dugger B . Prevalence of Submandibular Gland Synucleinopathy in Parkinson's Disease, Dementia with Lewy Bodies and other Lewy Body Disorders. J Parkinsons Dis. 2016; 6(1):153-63. PMC: 5498170. DOI: 10.3233/JPD-150680. View

16.

Hattori H, Matsumoto M, Iwai K, Tsuchiya H, Miyauchi E, Takasaki M . The tau protein of oral epithelium increases in Alzheimer's disease. J Gerontol A Biol Sci Med Sci. 2002; 57(1):M64-70. DOI: 10.1093/gerona/57.1.m64. View

17.

Ikonomovic M, Klunk W, Abrahamson E, Mathis C, Price J, Tsopelas N . Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain. 2008; 131(Pt 6):1630-45. PMC: 2408940. DOI: 10.1093/brain/awn016. View

18.

Ashton N, Ide M, Scholl M, Blennow K, Lovestone S, Hye A . No association of salivary total tau concentration with Alzheimer's disease. Neurobiol Aging. 2018; 70:125-127. DOI: 10.1016/j.neurobiolaging.2018.06.014. View

19.

Culp D, Graham L, Latchney L, Hand A . Rat sublingual gland as a model to study glandular mucous cell secretion. Am J Physiol. 1991; 260(6 Pt 1):C1233-44. DOI: 10.1152/ajpcell.1991.260.6.C1233. View

20.

Shi M, Sui Y, Peskind E, Li G, Hwang H, Devic I . Salivary tau species are potential biomarkers of Alzheimer's disease. J Alzheimers Dis. 2011; 27(2):299-305. PMC: 3302350. DOI: 10.3233/JAD-2011-110731. View