Reduced CSF CART in dementia with Lewy bodies

Abstract

Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease (AD). The underlying neurobiological mechanism of DLB is not fully understood and no generally accepted biomarkers are yet available for the diagnosis of DLB. In a recent MRI study, DLB patients displayed hypothalamic atrophy whereas this region was not affected in AD patients. Cocaine and amphetamine regulated transcript (CART) is a neuropeptide expressed selectively in neurons in the hypothalamus.Here, we found that CSF CART levels were significantly reduced by 30% in DLB patients (n=12) compared to controls (n=12) as well as to AD patients (n=14) using radioimmunoassay. Our preliminary results suggest that reduced CSF CART is a sign of hypothalamic dysfunction in DLB and that it may serve as a biomarker for this patient group.

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

“…This is the secondary point for the differential diagnosis. In addition, among other biomarker candidates, endogenous antioxidant CART is a highly promising one since deficits in serotonergic and dopaminergic pathways seem more pronounced in DLB patients, and CART can modulate these pathways [110] especially clinic practice shows that CART level in CSF is significantly decreased in DLB patients comparing to AD as well as healthy controls [90]. Combination of CART with the core markers would further increase the diagnostic accuracy.…”

“…Interestingly, CART level in CSF is decreased in AD patients comparing to healthy controls [90], indicating CART may be involved in the pathology or etiology of AD, it is worth further pursuing for their connection. Recently it has been shown that icariin, a flavonoid extracted from a Chinese herbal medicine Yin Yang Huo, also called Xian Ling Pi that has a protective role against Aβ42 neurotoxicity via up-regulation of CART in both mRNA and protein levels [91], suggesting that low levels of CART may be related to Aβ42 toxicity that is the main pathological event associated with Alzheimer's disease.…”

“…Although Lewy bodies have been described in the hypothalamus of DLB patients [108], extensive neuropathological studies of this region in DLB have not yet been reported. Using sensitive and a commercially available radioimmunoassay (RIA), Schultz K, et al [90] found that CSF CART levels were significantly reduced by 30% in DLB patients compared to controls as well as to AD patients. Even though this was not a large scale study, proper design including RIA assay controls and statistical analyses made the data convincing.…”

“…To evaluate and monitor the biomarker tests, except the standard (normal) values or value range should be listed, assay inner controls, kit internal as well as external controls should be included in each assay kit and the information may be necessary to be listed in the report. The assessment kit-associated study in the endocrinology, including the recent article regarding CSF CART expression determined by RIA or other methods may be good example [90,[113][114][115].…”

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“…Cart is involved in hypothalamic dysfunction in neurodegenerative disorders such as Dementia with Lewy Bodies (30). Reduced Sst levels have also been demonstrated in HD patient hypothalami (31).…”