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

Pereira, Joana B LU ; Kumar, Atul LU orcid ; Hall, Sara LU ; Palmqvist, Sebastian LU orcid ; Stomrud, Erik LU orcid ; Bali, Divya LU ; Parchi, Piero ; Mattsson-Carlgren, Niklas LU orcid ; Janelidze, Shorena LU and Hansson, Oskar LU orcid (2023) In Nature Aging 3(10). p.1201-1209
Abstract

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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Ageing, Diagnostic markers, Movement disorders
in
Nature Aging
volume
3
issue
10
pages
9 pages
publisher
Springer
external identifiers
  • scopus:85171461507
  • pmid:37723208
DOI
10.1038/s43587-023-00478-y
language
English
LU publication?
yes
id
6c1ad0f0-4e63-4c3d-b502-816e23f8dae1
date added to LUP
2023-09-20 11:55:17
date last changed
2024-04-21 20:35:29
@article{6c1ad0f0-4e63-4c3d-b502-816e23f8dae1,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Pereira, Joana B and Kumar, Atul and Hall, Sara and Palmqvist, Sebastian and Stomrud, Erik and Bali, Divya and Parchi, Piero and Mattsson-Carlgren, Niklas and Janelidze, Shorena and Hansson, Oskar}},
  keywords     = {{Ageing; Diagnostic markers; Movement disorders}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{10}},
  pages        = {{1201--1209}},
  publisher    = {{Springer}},
  series       = {{Nature Aging}},
  title        = {{DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease}},
  url          = {{http://dx.doi.org/10.1038/s43587-023-00478-y}},
  doi          = {{10.1038/s43587-023-00478-y}},
  volume       = {{3}},
  year         = {{2023}},
}