title: Alpha-synuclein levels in blood plasma decline with healthy aging.
abstract: There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Otfried-Müller-Strasse 27, 72076 Tübingen, Germany.
authors.forename: Niklas K U
authors.initials: NK
authors.lastname: Koehler
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Stransky
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Meyer
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Gaertner
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Shing
authors.affiliation: Zentrum für Klinische Transfusionsmedizin, Otfried-Müller-Strasse 4, 72076 Tübingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Schnaidt
authors.affiliation: Laboratory for Cellular Dynamics, Max-Planck-Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen, Germany; Department of Biological Chemistry (CIQUIBIC, CONICET), School of Chemical Sciences, National University of Córdoba, Haya de la Torrey Medina Allende, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Celej
authors.affiliation: Laboratory for Cellular Dynamics, Max-Planck-Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen, Germany.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jovin
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany; Center of Old Age Psychiatry, Psychiatric University Hospital, Wilhelm Klein-Strasse 27, CH-4012 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Leyhe
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany; German Center for Neurodegenerative Diseases (DZNE), Otfried-Müller-Strasse 27, 72076 Tübingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Laske
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany.
authors.forename: Anil
authors.initials: A
authors.lastname: Batra
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Buchkremer
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Fallgatter
authors.affiliation: Zentrum für Klinische Transfusionsmedizin, Otfried-Müller-Strasse 4, 72076 Tübingen, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Wernet
authors.affiliation: Department of Psychiatry and Psychotherapy, Eberhard-Karls-University Tübingen, Calwerstr. 14, 72076 Tübingen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Richartz-Salzburger
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D005786:Gene Expression Regulation; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D051844:alpha-Synuclein / Q000097:blood*
chemical_list: D015415:Biomarkers; C497604:SNCA protein, human; D051844:alpha-Synuclein
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