Saliva levels of Abeta 1-42 as potential biomarker of Alzheimer ’ s disease : a pilot study

Background: Simple, non-invasive tests for early detection of degenerative dementia by use of biomarkers are urgently required. However, up to the present, no validated extracerebral diagnostic markers for the early diagnosis of Alzheimer disease (AD) are available. The clinical diagnosis of probable AD is made with around 90% accuracy using modern clinical, neuropsychological and imaging methods. A biochemical marker that would support the clinical diagnosis and distinguish AD from other causes of dementia would therefore be of great value as a screening test. A total of 126 samples were obtained from subjects with AD, and age-sex-matched controls. Additionally, 51 Parkinson’s disease (PD) patients were used as an example of another neurodegenerative disorder. We analyzed saliva and plasma levels of b amyloid (Ab) using a highly sensitive ELISA kit. Results: We found a small but statistically significant increase in saliva Ab42 levels in mild AD patients. In addition, there were not differences in saliva concentration of Ab42 between patients with PD and healthy controls. Saliva Ab40 expression was unchanged within all the studied sample. The association between saliva Ab42 levels and AD was independent of established risk factors, including age or Apo E, but was dependent on sex and functional capacity. Conclusions: We suggest that saliva Ab42 levels could be considered a potential peripheral marker of AD and help discrimination from other types of neurodegenerative disorders. We propose a new and promising biomarker for early AD. Background With increasing life expectancy across the world, Alzheimer’s disease (AD), the most common cause of dementia, is a rapidly growing socioeconomic and medical problem. AD diagnosis is time consuming and requires a combination of clinical assessment, psychological testing, imaging and exclusion of other neurological disorders. In light of these facts, a molecular biomarker that could identify and classify AD would be particularly useful in order to confirm the diagnosis, to perform epidemiological screening, to identify distinct groups of patients, to predict the outcome of the disease, and to monitor its progression and its sensitivity to treatment. In fact, lack of tools to detect preclinical AD has been suggested to be one of the main obstacles for the development of new treatments [1]. The ideal biomarker for AD should detect a fundamental feature of neuropathology: it should be as sensitive and specific as the clinical diagnosis, reliable, reproducible, simple to perform, inexpensive and non-invasive (studies on blood, urine, saliva, or buccal scrapings). Moderately invasive tests (skin, rectal biopsies, bone marrow samples, or cerebrospinal fluid -CSF-) or cerebral biopsy, are inconvenient for routine clinical practice. In humans, in addition to the classical accumulation in the brain, amyloid-beta protein (Ab) deposits are found in peripheral regions, including skin [2], nasal mucosa [3], and the lacrimal [4], and lingual glands [5]. The use of human salivary gland biopsies has been recently described as a tool for research on familial amyloidotic polyneuropathy (FAD) [6], and on AD [7] because both amyloid precursor protein (APP) and Ab are expressed in human salivary epithelial cells [7]. Saliva is produced from salivary glands and mucous membranes and, as a biological fluid, is simple to obtain. Additionally, salivary levels may reflect changes in CSF * Correspondence: carroeva@yahoo.es Neurodegenerative Diseases Biomedical Research Center (CIBERNED), Madrid, Spain Full list of author information is available at the end of the article Bermejo-Pareja et al. BMC Neurology 2010, 10:108 http://www.biomedcentral. com/1471-2377/10/108 © 2010 Bermejo-Pareja et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. [8]. Recent studies showed association of activity and levels of salivary acetylcholinesterase (AChE) with AD [9]. These findings may prove to be a useful marker of central cholinergic activity which is a key event in the biochemistry of AD. The majority of the studies of accepted AD biomarkers to date have been carried out using samples of CSF obtained by lumbar puncture [10]. This is an invasive procedure that is particularly unpleasant for the subject and for which explicit consent is required. Recently, it has been shown that identification of blood biomarkers may allow the development of tests for AD [11,12]. In this study, we report that significant and reproducible levels of salivary Ab42 can be detected in subjects and there is a specific correlation with development of AD pathology.