Abstract
BackgroundThe search for new Alzheimer’s disease (AD) cerebrospinal fluid (CSF) and blood biomarkers with potential pathophysiological and clinical relevance continues, as new biomarkers might lead to improved early and differential diagnosis, monitoring of disease progression and might even identify new druggable targets. Melatonin might be an interesting biomarker as an inverse correlation between CSF melatonin levels, and severity of the neuropathology as measured by Braak stages has been described. Melatonin can be measured in different body fluids, such as CSF, blood, saliva and urine.ObjectivesThe aim of this systematic review was to review all available studies regarding melatonin levels in different body fluids in the AD continuum and give an extensive overview of reported outcomes.MethodsWe included papers comparing melatonin levels between healthy controls and human patients belonging to the AD continuum. A systematic search of PubMed and Web of Science led to inclusion of 20 full-length English papers following exclusion of duplicates.ResultsThis systematic literature search showed that disruptions in melatonin levels occur with age, but also in AD when compared to age-matched controls. Night-time melatonin levels were found to be lower in CSF and blood of AD patients as compared to controls. Literature was not conclusive regarding alterations in blood daytime melatonin levels or regarding saliva melatonin in AD patients. Decreased total and night-time melatonin production has been described in urine of AD patients.ConclusionOur systematic review shows evidence for disruptions in (night-time) melatonin levels in AD as compared to age-matched controls. Although more studies are needed to understand the contribution of disruption of the melatonergic system to the pathophysiology of AD, the potential anti-AD effects that have been attributed to melatonin, renders research on this topic relevant for the discovery of potential future treatment effects of melatonin for AD. The use of melatonin as potential blood biomarker for disease progression should also be further investigated.
Highlights
The search for new Alzheimer’s disease (AD) cerebrospinal fluid (CSF) and blood biomarkers with potential pathophysiological and clinical relevance continues, as new biomarkers might lead to improved early and differential diagnosis, monitoring of disease progression and might even identify new druggable targets
This systematic literature search showed that disruptions in melatonin levels occur with age, and in AD when compared to age-matched controls
We provided broad coverage of patient eligibility, including patients eligible based on National Institute on Aging and Alzheimer Association (NIA-AA) criteria [13, 14], National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria [15], Diagnostic and Statistical Manual for Mental Disorders (DSM) III and IV criteria [16, 17] or Petersen criteria for Mild cognitive impairment (MCI) [18]
Summary
The search for new Alzheimer’s disease (AD) cerebrospinal fluid (CSF) and blood biomarkers with potential pathophysiological and clinical relevance continues, as new biomarkers might lead to improved early and differential diagnosis, monitoring of disease progression and might even identify new druggable targets. Alzheimer’s disease (AD), a currently incurable condition, is the most prevalent cause of dementia, accounting for 60–70% of cases [1, 2]. Amongst which cerebrospinal fluid (CSF) amyloid-β (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau), are used for early and differential AD diagnosis [4, 5]. The search for new CSF and blood biomarkers with potential pathophysiological and clinical relevance continues, as new biomarkers might lead to improved early and differential diagnosis, monitoring of disease progression and might even identify new druggable targets
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