Early neuropathological Alzheimer's changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels

Abstract

Neuropathology is the most reliable criterion for diagnosing Alzheimer's disease (AD). A well-established system for staging the spread of neuropathological changes in AD is available. The clinical use of a biomarker that reflects the neuropathological change occurring in brain tissue has not yet been established. Melatonin is a product that plays not only a major role in the regulation of the circadian rhythms but may also exert neuroprotective effects in AD. Melatonin levels were determined in ventricular postmortem cerebrospinal fluid (CSF) of 121 subjects. Braak staging and a modified Braak staging for cortex (MBSC) were used to evaluate the severity of AD neuropathology. The present study revealed that not only the Braak stages of AD, but also the MBSC were negatively correlated with CSF melatonin levels. By using MBSC, we now demonstrate for the first time that CSF melatonin levels were significantly decreased in the aged individuals with early neuropathological changes in the temporal cortex, where the AD process starts. Those individuals that did not have any neurofibrillary tangle (NFT) or neuritic plaque (NP) in the temporal cortex, had much higher melatonin levels (287 +/- 68 and 280 +/- 64 pg/mL, respectively) than those individuals that had a few NFTs and NPs (82 +/- 4 and 39 +/- 8 pg/mL, respectively) in the temporal cortex. These results suggest that the decrease in CSF melatonin levels may be an early event in the development of AD possibly occurring even before the clinical symptoms.

Endogenous Melatonin Increases in Cerebrospinal Fluid of Patients after Severe Traumatic Brain Injury and Correlates with Oxidative Stress and Metabolic Disarray

“…Moreover, samples were obtained from the cranial CSF, which is comparable to the ventricular CSF obtained from TBI patients. Other studies (Table 3) have not obtained cranial CSF for control patient use, with the exception of three studies which used the ventricular CSF obtained from postmortem patients (Liu et al, 1999;Wu et al, 2003;Zhou et al, 2003), and one recent study using endoscopic sampling techniques (Longatti et al, 2007). In our study, the procedures for melatonin measurement were maintained consistently across the TBI and control patient populations, and hence the observed increase of endogenous CSF melatonin levels post-TBI is reliable.…”

Alzheimer’s Disease: Focus on the Neuroprotective Role of Melatonin

“…Studies of melatonin levels in AD patients reveal that they are lower in AD patients compared to age matched controls [73][74][75][76]. Decreased CSF melatonin levels in AD patients were attributed to decreased melatonin production rather than to diluting effects of CSF.…”

“…Decreased CSF melatonin levels in AD patients were attributed to decreased melatonin production rather than to diluting effects of CSF. CSF melatonin levels decreased even in preclinical stages (Braak stage-1) when patients did not yet manifest cognitive impairment, suggesting that a reduction in CSF melatonin may be an early marker for the first stages of AD [76,77]. The decrease of melatonin levels in AD has also been attributed to defective retino-hypothalamic tract or suprachiasmatic nucleus-pineal connections [78].…”

Mitochondrial Disorders Therapy: The Utility of Melatonin~!2009-11-18~!2010-01-21~!2010-06-23~!

“…In AD patients melatonin levels are decreased in blood and cerebrospinal fluid (CSF) and that reduction seems to parallel the progression of AD neuropathology [175,176]. Moreover, CSF melatonin levels are already decreased in pre-clinical AD individuals [175].…”