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Autoimmunity in Lewy body dementia Lewy body dementia (LBD) is a brain disease that leads to progressive decline in thinking, movement, and independent function. It results from the build-up of microscopic deposits called Lewy bodies, which develop from the aggregation of a misfolded protein called α-synuclein. Gate et al . observed immune cells known as T cells in the brains of LBD patients (see the Perspective by Krot and Rolls). Genomics analysis revealed that T cells traffic to the LBD brain and are associated with neuronal damage. When stimulated with α-synuclein, LBD patient T cells secrete an inflammatory protein known to damage neurons. These findings suggest an unexpected detrimental role of the immune system in LBD. —SMH

Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease and affects 1% of the population above 60 years old. Although Parkinson’s disease commonly manifests with motor symptoms, a majority of patients with Parkinson’s disease subsequently develop cognitive impairment, which often progresses to dementia, a major cause of morbidity and disability. Parkinson’s disease is characterized by α-synuclein accumulation that frequently associates with amyloid-β and tau fibrils, the hallmarks of Alzheimer’s disease neuropathological changes; this co-occurrence suggests that onset of cognitive decline in Parkinson’s disease may be associated with appearance of pathological amyloid-β 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 Alzheimer’s disease. Given the known association of microglial activation with advancing Parkinson’s disease, we investigated whether CSF and/or plasma sTREM2 differed between CSF biomarker-defined Parkinson’s disease participant subgroups. In this cross-sectional study, we examined 165 participants consisting of 17 cognitively normal elderly subjects, 45 patients with Parkinson’s disease with no cognitive impairment, 86 with mild cognitive impairment, and 17 with dementia. Stratification of subjects by CSF amyloid-β and tau levels revealed that CSF sTREM2 concentrations were elevated in Parkinson’s disease subgroups with a positive tau CSF biomarker signature, but not in Parkinson’s disease subgroups with a positive CSF amyloid-β biomarker signature. These findings indicate that CSF sTREM2 could serve as a surrogate immune biomarker of neuronal injury in Parkinson’s disease.

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