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

• Published in: NPJ Parkinson's Disease Vol. 10; no. 1; pp. 157 - 9
• Main Authors: Muñoz-Lopetegi, Amaia, Baiardi, Simone, Balasa, Mircea, Mammana, Angela, Mayà, Gerard, Rossi, Marcello, Serradell, Mónica, Zenesini, Corrado, Ticca, Alice, Santamaria, Joan, Dellavalle, Sofia, Gaig, Carles, Iranzo, Alex, Parchi, Piero
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1689/364; 692/53/2423; Alzheimer's disease; Behavior disorders; Biomarkers; Biomedical and Life Sciences; Biomedicine; Neurodegeneration; Neurology; Neurosciences; Pathology; REM sleep
• ISSN: 2373-8057; 2373-8057
• DOI: 10.1038/s41531-024-00770-7

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 (Aβ 42 and Aβ 40 ), 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 Aβ 42 /Aβ 40 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/Aβ 42 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/Aβ 42 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.