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CSF alpha-MSH in dementia of the Alzheimer type
1Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD 20892.
Abstract:
We measured CSF alpha-melanocyte stimulating hormone-like immunoreactivity (alpha-MSH-LI) in 35 patients with dementia of the Alzheimer type (DAT) and in 27 healthy control subjects. Mean alpha-MSH-LI concentration was significantly decreased in DAT patients as compared with age-matched controls. However, when the DAT patients were analyzed according to age at onset of dementia or presence of extrapyramidal signs, alpha-MSH-LI concentrations remained significantly lower than in controls only in DAT patients with late onset of dementia (greater than 65 years of age). No correlation was found between alpha-MSH levels and degree of mental impairment. A significant negative correlation was found between CSF concentrations of alpha-MSH and homovanillic acid in the group of all DAT patients (p less than 0.001). These results suggest that hypothalamic neurons which produce pro-opiomelanocortin-related peptides may be involved in Alzheimer's disease.
Insights
Levels of alpha-melanocyte stimulating hormone-like immunoreactivity (alpha-MSH-LI) were lower in Alzheimer's disease patients, particularly those with late-onset dementia. This suggests a potential role for pro-opiomelanocortin peptides in Alzheimer's disease pathogenesis.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder.
- The role of neuropeptides in AD pathogenesis is not fully understood.
Purpose of the Study:
- To investigate cerebrospinal fluid (CSF) alpha-melanocyte stimulating hormone-like immunoreactivity (alpha-MSH-LI) levels in patients with dementia of the Alzheimer type (DAT).
- To explore the relationship between alpha-MSH-LI levels and clinical characteristics of DAT, including age at onset and extrapyramidal signs.
Main Methods:
- CSF samples were collected from 35 DAT patients and 27 healthy controls.
- Alpha-MSH-LI concentrations were measured using radioimmunoassay.
- Correlations with clinical data and homovanillic acid levels were analyzed.
Main Results:
- Mean alpha-MSH-LI concentration was significantly decreased in DAT patients compared to controls.
- This decrease was significant only in late-onset DAT patients (onset > 65 years).
- No correlation was found between alpha-MSH levels and the degree of cognitive impairment.
- A significant negative correlation was observed between CSF alpha-MSH and homovanillic acid levels in DAT patients.
Conclusions:
- Hypothalamic neurons producing pro-opiomelanocortin-related peptides may be implicated in Alzheimer's disease.
- Reduced alpha-MSH-LI may be a specific biomarker for late-onset DAT.
- Further research is warranted to elucidate the precise role of these peptides in AD pathophysiology.