Kininogen-1 Protein Linked to Early Cognitive Impairment in Parkinson’s

Cognitive impairment is a common feature in Parkinson's disease (PD), associated with increased morbidity and mortality. An ongoing area of PD studies is the search for biomarkers that can provide prognostic information about cognitive impairment and other symptoms.

Cognitive impairment is a common non-motor symptom of Parkinson’s disease. Two distinct subtypes of cognitive dysfunction have been suggested in PD, including frontal executive dysfunction associated with dopaminergic loss, and the posterior/temporal subtype that affects visuospatial and semantic fluency function and correlates with cholinergic loss.

Clinical Neuroscientists at the Karolinska Institutet (Stockholm, Sweden) and their colleagues recruited 405 persons in the PD cohort of the AETIONOMY project in six university hospitals in France, Germany, and Sweden, between September 2015 and December 2017, including 251 patients with idiopathic PD, 25 with familial PD, 39 persons at risk for PD, and 90 healthy controls. Seventy-four Idiopathic PD patients with available cerebrospinal fluid (CSF) were included in the analyses.

A suspension bead array procedure was performed, utilizing polyclonal rabbit antibodies generated within the Human Protein Atlas project targeting 216 proteins. Proteins were selected either based on potential association to PD according to literature or by the teams’s previous neuroproteomic efforts. As a validation procedure, levels of kininogen in CSF were measured using a commercial enzyme‐linked immunosorbent assay (ELISA) kit (Abcam, Cambridge, UK). Dilution ratio was 1:100 and absorbance was measured by a Tecan Spark 10‐M plate reader (Tecan Group Ltd., Männedorf, Switzerland).

The team reported that in initial statistical analyses, they identified three proteins that were present at significantly higher levels in the CSF of those with low scores: kininogen-1 (KNG1), a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1), and kallikrein‐6 (KLK6). In subsequent analyses, which made statistical adjustments for possible confounding factors, KNG1 was significantly predictive of the Repeatable Battery for the Assessment of the Neuropsychological Status (RBANS score); that is, individuals with high KNG1 levels in their CSF were statistically more likely to have low RBANS scores. The other two proteins were not significantly associated with the RBANS score in these models.

The authors concluded that the results of a high‐throughput antibody‐based proteomic approach for the analysis of CSF markers related to early signs of cognitive impairment in PD and found that KNG1 levels in CSF were altered in PD patients with RBANS total score of low average level or less. The study was published in the November, 2020 issue of the journal Movement Disorders.

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