Liu R-Y, Zhou J-N, Van Heerkhuize J, Hofman MA, Swaab DFDecreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer's disease, and apolipoprotein E-e4/4 genotype. J Clin Endocrinol Metab 84:323-327

Netherlands Institute for Brain Research, Amsterdam.
Journal of Clinical Endocrinology &amp Metabolism (Impact Factor: 6.21). 02/1999; 84(1):323-7. DOI: 10.1210/jc.84.1.323
Source: PubMed


Sleep disruption, nightly restlessness, sundowning, and other circadian disturbances are frequently seen in Alzheimer's disease (AD) patients. Changes in the suprachiasmatic nucleus and pineal gland are thought to be the biological basis for these behavioral disturbances. Melatonin is the main endocrine message for circadian rhythmicity from the pineal. To determine whether melatonin production was affected in AD, melatonin levels were determined in the cerebrospinal fluid (CSF) of 85 patients with AD (mean age, 75 +/- 1.1 yr) and in 82 age-matched controls (mean age, 76 +/- 1.4 yr). Ventricular postmortem CSF was collected from clinically and neuropathologically well defined AD patients and from control subjects without primary neurological or psychiatric disease. In old control subjects (>80 yr of age), CSF melatonin levels were half of those in control subjects of 41-80 yr of age [176 +/- 58 (n = 29) and 330 +/- 66 (n = 53) pg/mL, respectively; P = 0.016]. We did not find a diurnal rhythm in CSF melatonin levels in control subjects. In AD patients the CSF melatonin levels were only one fifth (55 +/- 7 pg/mL) of those in control subjects (273 +/- 47 pg/mL; P = 0.0001). There was no difference in the CSF melatonin levels between the presenile (42 +/- 11 pg/mL; n = 21) and the senile (59 +/- 8 pg/mL; n = 64; P = 0.35) AD patients. The melatonin level in AD patients expressing apolipoprotein E-epsilon3/4 (71 +/- 11 pg/mL) was significantly higher than that in patients expressing apolipoprotein E-epsilon4/4 (32 +/- 8 pg/ml; P = 0.02). In the AD patients no significant correlation was observed between age of onset or duration of AD and CSF melatonin levels. In the present study, a dramatic decrease in the CSF melatonin levels was found in old control subjects and even more so in AD patients. Whether supplementation of melatonin may indeed improve behavioral disturbances in AD patients should be investigated.

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    • "Melatonin has beneficial effects on Alzheimer's disease (AD). AD patients show disturbed circadian rhythms and diminished CSF melatonin levels [102]. Changes in the SCN and pineal gland could be the biological basis for these behavioral disturbances. "
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    ABSTRACT: The adaptation of species to the environment in which they live is accomplished by so-called "clocks" that allow the biological, physiological, metabolic and behavioral system to correct any development during the day. The alteration of those 'clocks' (circadian rhythms) shows a strong relationship with organic disorders such as neurodegenerative diseases. Many studies show that oxidative stress combined with pro-inflammatory mechanisms, play a key role in the development of neurodegenerative diseases and psychiatric disorders. Oxidative stress is fought by many antioxidant molecules. Melatonin, a hallmark of circadian rhythm functionality, is a natural antioxidant with a circadian secretion pattern. The mechanisms involved in the antioxidant properties of melatonin are complex but its depletion or lack unequivocally leads to cell damage. This process is also linked to the disruption of the circadian rhythm. A disrupted circadian rhythm followed by oxidative stress and inflammatory processes could be the pathophysiological basis for several disorders of the central nervous system. In the current review we will analyze those interactions. We will focus on the relationship between melatonin and its light/dark rhythms of secretion and how the antioxidant properties of melatonin opens a new therapeutic hope against central nervous system disorders.
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    • "As soon as age-related reductions of melatonin become more profound, numerous changes are observed (Hardeland, 2012), among these considerable alterations in the immune system, as summarized earlier (Cardinali et al., 2008a). Decreased levels of melatonin are not only observed in pineal gland, blood and some other body fluids, but also in the cerebrospinal fluid (Brown et al., 1979; Liu et al., 1999). As long as a melatonin rhythm is still detectable in elderly individuals, the nocturnal peak of plasma melatonin is frequently phase-advanced relative to young subjects, indicating changes in the circadian oscillator system (Skene and Swaab, 2003). "

    • "It is noteworthy that neurodegeneration involves the NBM since the early phases of AD (Mesulam et al., 2004) with consequent SCN dysfunction (Bliwise, 2004). Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, AD, and apolipoprotein E-ε4 homozygote genotype have been found as well (Liu et al., 1999). Disruption of the circadian distribution of motor activity and of the basal temperature (Satlin et al., 1995), such as temporal variation in pain and mood in the evening hours (Bachman and Rabins, 2006), which are biological patterns of dementia, possibly explains some cases of sundown syndrome. "
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    ABSTRACT: Abstract Prevalence studies suggest that Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common dementing illnesses in the elderly. The aim of this narrative review was to provide data on sleep-related behaviors in AD and DLB. This paper contains arguments, with a clinical approach, on both circadian rhythm changes and dissociated states of wakefulness and sleep in these two conditions.
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