Plasma Neurofilament Light Chain predicts cognitive progression in prodromal and clinical dementia with Lewy Bodies

Padovani, Alessandro; Imarisio, Alberto; Carrarini, Claudia; Russo, Mirella; Masciocchi, Stefano; Gipponi, Stefano; Cottini, Elisabetta; Aarsland, Dag; Zetterberg, Henrik; Ashton, Nicholas J.; Hye, Abdul; Bonanni, Laura

doi:10.1101/2021.03.19.21253993

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Future research needs to clarify whether misfolded α-syn by RT-QuIC will serve as a state biomarker, while other markers may better serve as stage markers. For example, recent data shows the potential of the neurofilament light chain (NFL) in plasma as a stage marker (Pilotto et al, 2021).…”

Section: References Numbermentioning

confidence: 99%

Misfolded alpha-synuclein detection by RT-QuIC in dementia with lewy bodies: a systematic review and meta-analysis

Peña-Bautista¹,

Kumar

Baquero

et al. 2023

Front. Mol. Biosci.

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Introduction: Dementia with Lewy Bodies (DLB) is the second most common cause of neurodegenerative dementia after Alzheimer’s disease (AD), but the field is still lacking a specific biomarker for its core pathology: alpha synuclein (α-syn). Realtime quaking induced conversion (RT-QuIC) has recently emerged as a strong biomarker candidate to detect misfolded α-syn in DLB. However, the variability in the parameters of the technique and the heterogeneity of DLB patients make the reproducibility of the results difficult. Here, we provide an overview of the state-of-the-art research of α-syn RT-QuIC in DLB focused on: (1) the capacity of α-syn RT-QuIC to discriminate DLB from controls, Parkinson’s disease (PD) and AD; (2) the capacity of α-syn RT-QuIC to identify prodromal stages of DLB; and (3) the influence of co-pathologies on α-syn RT-QuIC’s performance. We also assessed the influence of different factors, such as technical conditions (e.g., temperature, pH, shaking-rest cycles), sample type, and clinical diagnosis versus autopsy confirmation.Methods: We conducted a systematic review following the PRISMA guidelines in August 2022, without any limits in publication dates. Search terms were combinations of “RT-QuIC” and “Lewy Bodies,” “DLB” or “LBD”.Results: Our meta-analysis shows that α-syn RT-QuIC reaches very high diagnostic performance in discriminating DLB from both controls (pooled sensitivity and specificity of 0.94 and 0.96, respectively) and AD (pooled sensitivity and specificity of 0.95 and 0.88) and is promising for prodromal phases of DLB. However, the performance of α-syn RT-QuIC to discriminate DLB from PD is currently low due to low specificity (pooled sensitivity and specificity of 0.94 and 0.11). Our analysis showed that α-syn RT-QuIC’s performance is not substantially influenced by sample type or clinical diagnosis versus autopsy confirmation. Co-pathologies did not influence the performance of α-syn RT-QuIC, but the number of such studies is currently limited. We observed technical variability across published articles. However, we could not find a clear effect of technical variability on the reported results.Conclusion: There is currently enough evidence to test misfolded α-syn by RT-QuIC for clinical use. We anticipate that harmonization of protocols across centres and advances in standardization will facilitate the clinical establishment of misfolded α-syn detection by RT-QuIC.

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Section: References Numbermentioning

confidence: 99%

Misfolded alpha-synuclein detection by RT-QuIC in dementia with lewy bodies: a systematic review and meta-analysis

Peña-Bautista¹,

Kumar

Baquero

et al. 2023

Front. Mol. Biosci.

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“…This cross-sectional study included consecutive patients with a clinical diagnosis of AD [7], dementia or prodromal Lewy bodies (DLB) [8] or early stages of frontotemporal dementia (FTD) [9] who underwent CSF assessment at the Neurology Unit of Brescia. All patients underwent routine blood analyses, magnetic resonance imaging (MRI), a standardized full cognitive and behavioral assessment, including the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) and an evaluation of basic and instrumental activities of daily living (ADL) [10]. Patients with mild cognitive impairment (MCI) or mild dementia were classified based on NIA-AA criteria and a diagnosis of AD was carried out according to CSF biomarker profile (see next section).…”

Section: Study Populationmentioning

confidence: 99%

Differences between plasma and CSF p-tau181 and p-tau231 in early Alzheimer’s disease

Parigi

Bonzi

battaglio

et al. 2021

Preprint

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Plasma phosphorylated tau species have been recently proposed as peripheral markers of Alzheimer s disease pathology. In this cross-sectional study incuding ninety-one subjects, plasma p-tau181 and p-tau231 levels were elevated in the early symptomatic stages of AD, with similar levels than those of CSF. Plasma p-tau231 and p-tau181 were strongly related to CSF tau and amyloid and exhibited a high accuracy, close to CSF p-tau231 and p-tau181, to identify AD already in the early stage of the disease. The findings might support the use as diagnostic and prognostic peripheral AD biomarkers in both research and clinical settings.

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Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium

et al. 2022

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The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.

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Plasma Neurofilament Light Chain predicts cognitive progression in prodromal and clinical dementia with Lewy Bodies

Cited by 3 publications

References 29 publications

Misfolded alpha-synuclein detection by RT-QuIC in dementia with lewy bodies: a systematic review and meta-analysis

Misfolded alpha-synuclein detection by RT-QuIC in dementia with lewy bodies: a systematic review and meta-analysis

Differences between plasma and CSF p-tau181 and p-tau231 in early Alzheimer’s disease

Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium

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