Late diagnosis is a problem in Parkinsonian syndromes. Today diagnosis is made when almost all dopaminergic neurons are lost. Now this Swedish study found a new sensitive biomarker finding these diseases even 3 years earlier than the symptoms are evident. It is possible that this biomarker could also indicate if a drug, like ATH434, could start reversing the disease process earlier than the present biomarkers.

Nat Aging

. 2023 Sep 18.

doi: 10.1038/s43587-023-00478-y. Online ahead of print.

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

Joana B Pereira ^{# 1 2}, Atul Kumar ^{# 2}, Sara Hall ^{2 3}, Sebastian Palmqvist ^{2 3}, Erik Stomrud ^{2 3}, Divya Bali ², Piero Parchi ^{4 5}, Niklas Mattsson-Carlgren ^{2 6 7}, Shorena Janelidze ², Oskar Hansson ^{8 9}

Affiliations expand

• PMID: 37723208

DOI: 10.1038/s43587-023-00478-y

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; P_FDR = 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.