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CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder

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We investigated the biomarker profile of neurodegeneration, Alzheimer's and Lewy body pathology in the CSF of 148 polysomnography-confirmed patients with isolated REM sleep behavior disorder (IRBD), a condition that precedes Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We assessed misfolded α-synuclein (AS) by RT-QuIC assay, amyloid-beta peptides (Aβ42 and Aβ40), phosphorylated tau (p-tau), and total tau (t-tau) by CLEIA and neurofilament light chain (NfL) by ELISA. We detected AS in 75.3% of patients, pathologically decreased Aβ42/Aβ40 ratio in 22.5%, increased p-tau in 15.5%, increased t-tau in 14.9%, and elevated NfL in 14.7%. After a mean follow-up of 2.48 ± 2.75 years, 47 (38.1%) patients developed PD (n = 24) or DLB (n = 23). At CSF collection, AS positivity [HR 4.05 (1.26-12.99), p = 0.019], mild cognitive impairment [3.86 (1.96-7.61), p < 0.001], and abnormal DAT-SPECT [2.31 (1.09-4.91), p < 0.030] were independent predictors of conversion to PD and DLB. Among the other CSF markers, only elevated p-tau/Aβ42 was predictive of conversion, although only to DLB and not as an independent variable. In IRBD, CSF AS assessment by RT-QuIC provides an added value in defining the risk of short-term conversion to PD and DLB independent of clinical and instrumental investigations. Positive Alzheimer's disease (AD) pathology markers and elevated NfL occur in a subgroup of patients, but p-tau/Aβ42 is the only marker that predicts short-term conversion to DLB. Longer follow-up is needed to assess if AD biomarkers predict the later development of PD and DLB in IRBD.

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npj Parkinson's Disease, 2024, vol. 10, num.1

# metadata.dc.rights[].value
cc-by (c)  Muñoz-Lopetegi, A. et al., 2024

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Articles publicats en revistes (Medicina)

# metadata.dc.title[].value
CSF markers of neurodegeneration Alzheimer’s and Lewy body pathology in isolated REM sleep behavior disorder