DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease

Pereira, Joana B (author): Karolinska Institutet,Karolinska Institute,Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups

Kumar, Atul (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups

Hall, Sara (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital

Palmqvist, Sebastian (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital

Stomrud, Erik (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital

Bali, Divya (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups

Mattsson-Carlgren, Niklas (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Skåne University Hospital

Janelidze, Shorena (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Clinical Memory Research,Lund University Research Groups

Hansson, Oskar (author): Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Department of Clinical Sciences, Malmö,Faculty of Medicine,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital

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Abstract Subject headings

The diagnosis of Parkinsonian disorders is currently based on clinical criteria, which have limited sensitivity until most dopaminergic neurons are lost. Here we show that cerebrospinal fluid levels of DOPA decarboxylase (DDC) (also known as aromatic L-amino acid decarboxylase) can accurately identify patients with Lewy body disease (LBD) (area under the curve (AUC) = 0.89; PFDR = 2.6 × 10-13) and are associated with worse cognitive performance (P < 0.05). We also found that DDC can detect preclinical LBD stages in clinically unimpaired individuals with a positive seed amplification α-synuclein assay (AUC = 0.81, P = 1.0 × 10-5) and that this biomarker could predict progression to clinical LBD over a 3-year period in preclinical cases (hazard ratio = 3.7 per s.d. change, confidence interval = 1.1-12.7). Moreover, DDC levels were also increased in atypical Parkinsonian disorders but not in non-Parkinsonian neurodegenerative disorders. These cerebrospinal fluid results were replicated in an independent cohort, where we also found that DDC levels in plasma could identify both LBD and atypical Parkinsonian disorders (AUC = 0.92, P = 1.3 × 10-14). Our results show that DDC might have a future role in clinical practice as a biomarker of dopaminergic dysfunction to detect Parkinsonian disorders even during the preclinical disease stages and predict their progression to clinical LBD.

By the author/editor: Pereira, Joana B; Kumar, Atul; Hall, Sara; Palmqvist, Sebas ...; Stomrud, Erik; Bali, Divya; show more...; Parchi, Piero; Mattsson-Carlgre ...; Janelidze, Shore ...; Hansson, Oskar; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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