Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease.docVIP

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Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease.doc

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Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

CerebrospinalFluidMelanin-ConcentratingHormone (MCH)andHypocretin-1(HCRT-1,Orexin-A)in Alzheimer’sDisease FrankM.Schmidt1*,JuergenKratzsch2,Hermann-JosefGertz1,MandyTittmann1,InaJahn1 ,Uta- CarolinPietsch3,UdoX.Kaisers3,JoachimThiery2,UlrichHegerl1,PeterScho¨nknecht1 1Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Leipzig, Germany, 2Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics,UniversityHospitalLeipzig,Leipzig,Germany,3DepartmentofAnesthesiologyandIntensiveCareMedicine,UniversityHospitalLeipzig,Leipzig,Germany Abstract Ancillary to decline in cognitive abilities, patients with Alzheimer’s disease (AD) frequently suffer from behavioural and psychologicalsymptomsofdementia(BPSD).Hypothalamicpolypeptidessuchasmelanin-concentratinghormone(MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impactoncognitiveperformance.ToinvestigatetheroleofMCHandHCRT-1inAD,cerebrospinalfluid(CSF)levelswere measuredin33patientswithADand33healthysubjects(HS)usingafluorescenceimmunoassay(FIA).Asignificantmain effect of diagnosis (F(1,62)=8.490, p,0.01) on MCH levels was found between AD (93.76613.47pg/mL) and HS (84.65611.40pg/mL).MCHcorrelatedwithT-tau(r=0.47;p,0.01)andP-tau(r=0.404;p,0.05)intheADbutnotintheHS. CSF-MCH correlated negatively with MMSE scores in the AD (r=20.362, p,0.05) and was increased in more severely affectedpatients(MMSE#20)comparedtoHS(p,0.001)andBPSD-positivepatientscomparedtoHS(p,0.05).InCSF-HCRT- 1, a significant main effect of sex (F(1,31)=4.400, p,0.05) with elevated levels in females (90.93617.37pg/mL vs. 82.73615.39pg/mL)wasfoundwhereasdiagnosisandthesex*diagnosisinteractionwerenotsignificant.Elevatedlevelsof MCHinpatientssufferingfromADandcorrelationwithTauandseverityofcognitiveimpairmentpointtowardsanimpact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-reg