title: Cerebrospinal fluid melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) in Alzheimer's disease.
abstract: Ancillary to decline in cognitive abilities, patients with Alzheimer's disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62) = 8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r = 0.47; p<0.01) and P-tau (r = 0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = -0.362, p<0.05) and was increased in more severely affected patients (MMSE≤20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31) = 4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Leipzig, Germany. frank.schmidt2@medizin.uni-leipzig.de
authors.forename: Frank M
authors.initials: FM
authors.lastname: Schmidt
authors.forename: Juergen
authors.initials: J
authors.lastname: Kratzsch
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gertz
authors.forename: Mandy
authors.initials: M
authors.lastname: Tittmann
authors.forename: Ina
authors.initials: I
authors.lastname: Jahn
authors.forename: Uta-Carolin
authors.initials: UC
authors.lastname: Pietsch
authors.forename: Udo X
authors.initials: UX
authors.lastname: Kaisers
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hegerl
authors.forename: Peter
authors.initials: P
authors.lastname: Schönknecht
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007028:Hypothalamic Hormones / Q000134:cerebrospinal fluid*; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D008297:Male; D008543:Melanins / Q000134:cerebrospinal fluid*; D009479:Neuropeptides / Q000134:cerebrospinal fluid*; D000068797:Orexins; D010907:Pituitary Hormones / Q000134:cerebrospinal fluid*; D012727:Sex Characteristics
chemical_list: C000596229:HCRT protein, human; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone