title: Serum and cerebrospinal fluid levels of transthyretin in Lewy body disorders with and without dementia.
abstract: Parkinson's disease (PD) without (non-demented, PDND) and with dementia (PDD), and dementia with Lewy bodies (DLB) are subsumed under the umbrella term Lewy body disorders (LBD). The main component of the underlying pathologic substrate, i.e. Lewy bodies and Lewy neurites, is misfolded alpha-synuclein (Asyn), and--in particular in demented LBD patients--co-occurring misfolded amyloid-beta (Abeta). Lowered blood and cerebrospinal fluid (CSF) levels of transthyretin (TTR)--a clearance protein mainly produced in the liver and, autonomously, in the choroid plexus--are associated with Abeta accumulation in Alzheimer's disease. In addition, a recent study suggests that TTR is involved in Asyn clearance. We measured TTR protein levels in serum and cerebrospinal fluid of 131 LBD patients (77 PDND, 26 PDD, and 28 DLB) and 72 controls, and compared TTR levels with demographic and clinical data as well as neurodegenerative markers in the CSF. Five single nucleotide polymorphisms of the TTR gene which are considered to influence the ability of the protein to carry its ligands were also analyzed. CSF TTR levels were significantly higher in LBD patients compared to controls. Post-hoc analysis demonstrated that this effect was driven by PDND patients. In addition, CSF TTR levels correlated negatively with CSF Abeta(1-42), total tau and phospho-tau levels. Serum TTR levels did not significantly differ among the studied groups. There were no relevant associations between TTR levels and genetic, demographic and clinical data, respectively. These results suggest an involvement of the clearance protein TTR in LBD pathophysiology, and should motivate to elucidate TTR-related mechanisms in LBD in more detail.
authors.affiliation: Center of Neurology, Department of Neurodegeneration and Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany. walter.maetzler@uni-tuebingen.d
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.forename: Youyong
authors.initials: Y
authors.lastname: Tian
authors.forename: Stephanie Maria
authors.initials: SM
authors.lastname: Baur
authors.forename: Tina
authors.initials: T
authors.lastname: Gauger
authors.forename: Bartholomäus
authors.initials: B
authors.lastname: Odoj
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schmid
authors.forename: Claudia
authors.initials: C
authors.lastname: Schulte
authors.forename: Christian
authors.initials: C
authors.lastname: Deuschle
authors.forename: Susanna
authors.initials: S
authors.lastname: Heck
authors.forename: Anja
authors.initials: A
authors.lastname: Apel
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D015331:Cohort Studies; D003704:Dementia / Q000097:blood* / Q000134:cerebrospinal fluid*; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D020961:Lewy Body Disease / Q000097:blood* / Q000134:cerebrospinal fluid*; D008024:Ligands; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010300:Parkinson Disease / Q000097:blood* / Q000134:cerebrospinal fluid*; D011110:Polymorphism, Genetic; D011228:Prealbumin / Q000096:biosynthesis* / Q000134:cerebrospinal fluid*
chemical_list: D001057:Apolipoproteins E; D008024:Ligands; D011228:Prealbumin