Finding useful biomarkers for Parkinson’s disease

Chen‐Plotkin, Alice S.; Albin, Roger L.; Alcalay, Roy N.; Babcock, Debra; Bajaj, Vikram S.; Bowman, Dubois; Buko, Alexander M.; Cedarbaum, Jesse M.; Chelsky, Daniel; Cookson, Mark; Dawson, Ted M.; Dewey, Richard B.; Foroud, Tatiana; Frasier, Mark; German, Dwight C.; Gwinn, Katrina; Huang, Xuemei; Kopil, Catherine; Kremer, Thomas; Lasch, Shirley; Marek, Kenneth; Marto, Jarrod A.; Merchant, Kalpana; Mollenhauer, Brit; Naito, Anna; Potashkin, Judith A.; Reimer, Alyssa; Rosenthal, Liana S.; Saunders‐Pullman, Rachel; Scherzer, Clemens R.; Sherer, Todd; Singleton, Andrew B.; Sutherland, Margaret; Thiele, Ines; Brug, Marcel van der; Keuren‐Jensen, Kendall Van; Vaillancourt, David E.; Walt, David R.; West, Andrew B.; Zhang, Jing

doi:10.1126/scitranslmed.aam6003

Cited by 132 publications

(93 citation statements)

References 33 publications

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“…Substantial biological heterogeneity underlies the clinical presentation and progression of PD and there is a significant need for markers that differentiate subgroups of PD patients in their rate of progression along cognitive and motor trajectories, or in the types of co-morbid disease (Chen-Plotkin et al, 2018). We report here that CSF sTREM2 is increased in PD patient subgroups with abnormal CSF tau concentration, with or without abnormal CSF Aβ concentration, and that this increase precedes cognitive impairment.…”

Section: Discussionmentioning

confidence: 75%

“…Identifying a biomarker that could help predict a change in cognitive function in PD would be a valuable tool for clinical management and outcome measure for clinical trials. Given the heterogeneous nature of PD, there is a significant unmet need for markers that could differentiate subgroups of PD patients that vary in rate of progression along cognitive and motor trajectories, or subgroups of PD patients with important differences in pathogenesis (Chen-Plotkin et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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CSF sTREM2 correlates with CSF tau in advancing Parkinson’s disease

Wilson

Swarovski

Linortner

et al. 2019

Preprint

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222 Introduction: 565 Participants and Methods: 966 Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD) and affects 1% of the population above 60 years old. Although PD commonly manifests with motor symptoms, a majority of patients with PD subsequently develop cognitive impairment which often progresses to dementia, a major cause of morbidity and disability. PD is characterized by α -synuclein accumulation that frequently associates with amyloid beta (Aβ) and tau fibrils, the hallmarks of AD neuropathologic changes; this cooccurrence suggests that onset of cognitive decline in PD may be associated with appearance of pathologic Aβ and/or tau. Recent studies have highlighted the appearance of the soluble form of the Triggering Receptor Expressed on Myeloid cells 2 (sTREM2) receptor in CSF during development of AD. Given the known association of microglial activation with advancing PD, we investigated whether CSF and/or plasma sTREM2 increased with progression to PD dementia. We examined 165 participants consisting of 17 cognitively normal elderly, 45 PD patients with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF Aβ and tau levels revealed that CSF sTREM2concentrations were elevated in PD subgroups with abnormal tau, but not Aβ, CSF concentration. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in PD that is associated with cognitive decline.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

CSF sTREM2 correlates with CSF tau in advancing Parkinson’s disease

Wilson

Swarovski

Linortner

et al. 2019

Preprint

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“…These include the heterogeneity of the clinical course of PD and the lack of biomarkers for diagnostic certainty and monitoring of disease progression. Development of tools for diagnosis and monitoring of disease progression beyond clinical assessments that are used by master clinicians will be critical to identify disease-modifying compounds that have small to modest but significant effects (10). An agent that halts disease progression may obviate the need to address these issues.…”

Section: Points To Considermentioning

confidence: 99%

Promising disease-modifying therapies for Parkinson’s disease

Dawson

2019

Sci. Transl. Med.

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“…Several recent reviews, for example, Algarni and Stoessl, have summarized the state of the art with regard to need for biomarkers for patient selection and monitoring of disease outcomes in PD clinical trials, and Chen‐Plotkin et al reviewed the necessity for rigor and discipline in the selection and validation of biomarkers for PD trials . Recent studies, including the Parkinson Progression Markers Initiative and others, have been able to shed light on the utility of dopamine transporter imaging (DaT) for excluding persons with symptoms and physical signs resembling PD from PD clinical trials.…”

Section: Six Main Categories Of Biomarkersmentioning

confidence: 99%

“…12 Several recent reviews, for example, Algarni and Stoessl, 13 have summarized the state of the art with regard to need for biomarkers for patient selection and monitoring of disease outcomes in PD clinical trials, and Chen-Plotkin et al reviewed the necessity for rigor and discipline in the selection and validation of biomarkers for PD trials. 14 persons with symptoms and physical signs resembling PD from PD clinical trials. However, because DaT imaging can also be abnormal in other parkinsonian syndromes, it cannot differentiate synucleinopathyrelated PD from other, related disorders.…”

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confidence: 99%