Serum neurofilament light chain as a surrogate of cognitive decline in sporadic and familial frontotemporal dementia

Silva-Spínola, Anuschka; Lima, Marisa; Leitão, Maria João; Durães, João; Tábuas‐Pereira, Miguel; Almeida, Maria Rosário; Santana, Isabel; Baldeiras, Inês

doi:10.1111/ene.15058

Cited by 18 publications

(12 citation statements)

References 55 publications

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“…These analytes could represent measures of the neuropathological AD features, where blood‐derived GFAP and p‐Tau181 are measures of Aβ burden [10, 18, 35], p‐Tau181 also of tauopathy [10, 17], and NfL of neurodegeneration [8, 17, 30, 35], similar to the scheme of the ATN classification for CSF. Therefore, under some circumstances, they could act as surrogates for the ATN scheme through a less invasive and less expensive method.…”

Section: Discussionmentioning

confidence: 99%

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Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia

Silva-Spínola

Lima

Leitão

et al. 2023

Euro J of Neurology

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Background and purpose: Blood-based biomarkers are promising tools for the diagnosis of Alzheimer disease (AD) at prodromal stages (mild cognitive impairment [MCI]) and are hoped to be implemented as screening tools for patients with cognitive complaints. In this work, we evaluated the potential of peripheral neurological biomarkers to predict progression to AD dementia and the relation between blood and cerebrospinal fluid (CSF) AD markers in MCI patients referred from a general neurological department.Methods: A group of 106 MCI patients followed at the Neurology Department of Coimbra University Hospital was included. Data regarding baseline neuropsychological evaluation, CSF levels of amyloid β 42 (Aβ42), Aβ40, total tau (t-Tau), and phosphorylated tau 181 (p-Tau181) were available for all the patients. Aβ42, Aβ40, t-Tau, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were determined in baseline stored serum and plasma samples by commercial SiMoA (Single Molecule Array) assays. Progression from MCI to AD dementia was assessed at follow-up (mean = 5.8 ± 3.4 years).Results: At baseline, blood markers NfL, GFAP, and p-Tau181 were significantly increased in patients who progressed to AD at follow-up (p < 0.001). In contrast, plasma Aβ42/40 ratio and t-Tau showed no significant differences between groups. NfL, GFAP, and p-Tau181 demonstrated good diagnostic accuracy to identify progression to AD dementia (area under the curve [AUC] = 0.81, 0.80, and 0.76, respectively), which improved when combined (AUC = 0.89). GFAP and p-Tau181 were correlated with CSF Aβ42. Association of p-Tau181 with NfL was mediated by GFAP, with a significant indirect association of 88% of the total effect. Conclusions: Our findings highlight the potential of combining blood-based GFAP, NfL, and p-Tau181 to be applied as a prognostic tool in MCI.

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Section: Discussionmentioning

confidence: 99%

“…have allowed for the reliable quantification of the CSF core AD proteins in peripheral blood, potentially reducing the need for a lumbar puncture during monitoring and/or screening of patients [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia

Silva-Spínola

Lima

Leitão

et al. 2023

Euro J of Neurology

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“…Brain imaging and several biofluid proteins have been proposed as biomarkers for both ALS and FTD (Al Shweiki et al , 2019; Ashton et al , 2021; Bellini et al , 2022; Benussi et al , 2019; Bian et al , 2008; Borroni et al , 2015; Bourbouli et al , 2017; Bright et al , 2019; Chouliaras et al , 2022; Das et al , 2022; Delaby et al , 2020; Eratne et al , 2022; Feneberg et al , 2018; Forgrave et al , 2019; Goncalves et al , 2017; Gonzalez-Garza et al , 2018; Hansson et al , 2019; Hu et al , 2013; Jiskoot et al , 2019; Katisko et al , 2021; Katisko et al , 2020; Krishnan et al , 2022; McCarthy et al , 2018; Meeter et al , 2017; Meeter et al , 2018; Niikado et al , 2019; Oeckl et al , 2022; Prado et al , 2018; Rossi et al , 2018; Sheikh-Bahaei et al , 2017; Silva-Spinola et al , 2022; Teunissen et al , 2016; Thijssen et al , 2022; Turner et al , 2009; van der Ende et al , 2020; Verde et al , 2021; Wilson et al , 2022; Xu et al , 2016). Among the proteins, noticeable are neurofilament light chain (NfL), TDP-43 and, phospho-tau, amyloid beta and glial fibrillary acidic protein (GFAP).…”

Section: Introductionmentioning

confidence: 99%

microRNA-based predictor for diagnosis of frontotemporal dementia

Magen

Warren

Heller

et al. 2020

Preprint

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Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder characterized by frontal and temporal lobe atrophy, typically manifesting with behavioural or language impairment. Because of its heterogeneity and lack of available diagnostic laboratory tests there can be a substantial delay in diagnosis. Cell-free, circulating, microRNAs are increasingly investigated as biomarkers for neurodegeneration, but their value in FTD is not yet established. In this study, we investigate microRNAs as biomarkers for FTD diagnosis. We performed next generation small RNA sequencing on cell-free plasma from 52 FTD cases and 21 controls. The analysis revealed the diagnostic importance of 20 circulating endogenous miRNAs in distinguishing FTD cases from controls. The study was repeated in an independent second cohort of 117 FTD cases and 35 controls. The combinatorial microRNA signature from the first cohort, precisely diagnosed FTD samples in a second cohort. To further increase the generalizability of the prediction, we implemented machine learning techniques in a merged dataset of the two cohorts, which resulted in a comparable or improved classification precision with a smaller panel of miRNA classifiers. In addition, there are intriguing molecular commonalities with cell free miRNA signature in ALS, a motor neuron disease that resides on a pathological continuum with FTD. However, the signature that describes the ALS-FTD spectrum is not shared with blood miRNA profiles of patients with multiple sclerosis. Thus, microRNAs are promising FTD biomarkers that might enable earlier detection of FTD and improve accurate identification of patients for clinical trials

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“…After an axonal injury or neuronal degeneration, NfL is released into interstitial fluid and eventually into CSF and plasma [56,57]. NfL levels are increased in frontotemporal dementia [58], small vessel disease [59], Parkinson's disease [60] and AD [61]. The results of crosssectional studies comparing plasma NfL concentrations and cognitive performance are mixed: some studies have found associations [62], whereas others did not [63,64].…”

Section: Peripheral-blood-based Measures Of Neuropathologymentioning

confidence: 99%

Developments in scalable strategies for detecting early markers of cognitive decline

et al. 2022

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Effective strategies for early detection of cognitive decline, if deployed on a large scale, would have individual and societal benefits. However, current detection methods are invasive or time-consuming and therefore not suitable for longitudinal monitoring of asymptomatic individuals. For example, biological markers of neuropathology associated with cognitive decline are typically collected via cerebral spinal fluid, cognitive functioning is evaluated from face-to-face assessments by experts and brain measures are obtained using expensive, non-portable equipment. Here, we describe scalable, repeatable, relatively non-invasive and comparatively inexpensive strategies for detecting the earliest markers of cognitive decline. These approaches are characterized by simple data collection protocols conducted in locations outside the laboratory: measurements are collected passively, by the participants themselves or by non-experts. The analysis of these data is, in contrast, often performed in a centralized location using sophisticated techniques. Recent developments allow neuropathology associated with potential cognitive decline to be accurately detected from peripheral blood samples. Advances in smartphone technology facilitate unobtrusive passive measurements of speech, fine motor movement and gait, that can be used to predict cognitive decline. Specific cognitive processes can be assayed using ‘gamified’ versions of standard laboratory cognitive tasks, which keep users engaged across multiple test sessions. High quality brain data can be regularly obtained, collected at-home by users themselves, using portable electroencephalography. Although these methods have great potential for addressing an important health challenge, there are barriers to be overcome. Technical obstacles include the need for standardization and interoperability across hardware and software. Societal challenges involve ensuring equity in access to new technologies, the cost of implementation and of any follow-up care, plus ethical issues.

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Serum neurofilament light chain as a surrogate of cognitive decline in sporadic and familial frontotemporal dementia

Cited by 18 publications

References 55 publications

Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia

Blood biomarkers in mild cognitive impairment patients: Relationship between analytes and progression to Alzheimer disease dementia

microRNA-based predictor for diagnosis of frontotemporal dementia

Developments in scalable strategies for detecting early markers of cognitive decline

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