Cerebrospinal fluid mitochondrial DNA in the Alzheimer's disease continuum

Cervera-Carles, Laura; Alcolea, Daniel; Estanga, Ainara; Ecay-Torres, Mirian; Izagirre, Andrea; Clerigué, Montserrat; García-Sebastián, Maite; Villanúa, Jorge; Escalas, Clàudia; Blesa, Rafael; Martínez-Lage, Pablo; Lleó, Alberto; Fortea, Juan; Clarimón, Jordi

doi:10.1016/j.neurobiolaging.2016.12.009

Cited by 29 publications

(24 citation statements)

References 23 publications

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“…Around 80% of NDD patients (n = 65) were diagnosed with dementia before death. Similar to studies in sporadic Creutzfeldt-Jakob disease 42 and AD dementia 27 , we observed significantly higher vCSF-cfmtDNA levels in patients diagnosed with dementia when compared to non-demented cases (TTEST p = 0.024, Fig. 1c).…”

Section: Vcsf-cfmtdna Is Increased In Patients Exhibiting Neocorticalsupporting

confidence: 88%

“…Previous literature 26 suggests that 'probable' AD cases (defined as those with low CSF amyloid beta 1-42 and elevated tau levels) and high-risk for AD individuals (defined as asymptomatic but with low CSF amyloid beta 1-42 ) exhibit significantly lower lumbar CSF cfmtDNA than controls. Conversely, a study of well-characterised AD patients reports significantly higher lumbar CSF cfmtDNA level than that of cognitively healthy controls 27 .…”

Section: Discussionmentioning

confidence: 91%

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Post-mortem ventricular cerebrospinal fluid cell-free-mtDNA in neurodegenerative disease

Lowes

Kurzawa‐Akanbi

Pyle

et al. 2020

Sci Rep

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Cell-free mitochondrial DNA (cfmtDNA) is detectable in almost all human body fluids and has been associated with the onset and progression of several complex traits. In-life assessments indicate that reduced cfmtDNA is a feature of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. However, whether this feature is conserved across all neurodegenerative diseases and how it relates to the neurodegenerative processes remains unclear. In this study, we assessed the levels of ventricular cerebrospinal fluid-cfmtDNA (vCSF-cfmtDNA) in a diverse group of neurodegenerative diseases (NDDs) to determine if the in-life observations of reduced cfmtDNA seen in lumbar CSF translated to the post-mortem ventricular CSF. To investigate further, we compared vCSF-cfmtDNA levels to known protein markers of neurodegeneration, synaptic vesicles and mitochondrial integrity. Our data indicate that reduced vCSF-cfmtDNA is a feature specific to Parkinson’s and appears consistent throughout the disease course. Interestingly, we observed increased vCSF-cfmtDNA in the more neuropathologically severe NDD cases, but no association to protein markers of neurodegeneration, suggesting that vCSF-cfmtDNA release is more complex than mere cellular debris produced following neuronal death. We conclude that vCSF-cfmtDNA is reduced in PD, but not other NDDs, and appears to correlate to pathology. Although its utility as a prognostic biomarker is limited, our data indicate that higher levels of vCSF-cfmtDNA is associated with more severe clinical presentations; suggesting that it is associated with the neurodegenerative process. However, as vCSF-cfmtDNA does not appear to correlate to established indicators of neurodegeneration or indeed indicators of mitochondrial mass, further work to elucidate its exact role is needed.

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Section: Vcsf-cfmtdna Is Increased In Patients Exhibiting Neocorticalsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 91%

Post-mortem ventricular cerebrospinal fluid cell-free-mtDNA in neurodegenerative disease

Lowes

Kurzawa‐Akanbi

Pyle

et al. 2020

Sci Rep

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“…CSF samples from the SPIN cohort have contributed to several international multicenter CSF biomarker studies [34][35][36][37][38]. The SPIN cohort has contributed to the characterization of different CSF biomarkers such as b-site APP-cleaving enzyme activity [39,40], sAPP-b [6,39,41], neurofilament light chain [41], YKL-40 [6,39,[41][42][43], progranulin [44], a panel of synaptic proteins [45], and mitochondrial DNA [46] in different neurodegenerative diseases. In addition, the collection of paired blood and CSF samples offers the possibility to investigate the correlation of biomarker levels between these two compartments [15,44].…”

Section: Resultsmentioning

confidence: 99%

The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: A data set for biomarker discovery and validation in neurodegenerative disorders

Alcolea

Clarimón

Carmona-Iragui

et al. 2019

A&D Transl Res & Clin Interv

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101

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Introduction The SPIN (Sant Pau Initiative on Neurodegeneration) cohort is a multimodal biomarker platform designed for neurodegenerative disease research following an integrative approach. Methods Participants of the SPIN cohort provide informed consent to donate blood and cerebrospinal fluid samples, receive detailed neurological and neuropsychological evaluations, and undergo a structural 3T brain MRI scan. A subset also undergoes other functional or imaging studies (video‐polysomnogram, 18F‐fluorodeoxyglucose PET, amyloid PET, Tau PET). Participants are followed annually for a minimum of 4 years, with repeated cerebrospinal fluid collection and imaging studies performed every other year, and brain donation is encouraged. Results The integration of clinical, neuropsychological, genetic, biochemical, imaging, and neuropathological information and the harmonization of protocols under the same umbrella allows the discovery and validation of key biomarkers across several neurodegenerative diseases. Discussion We describe our particular 10‐year experience and how different research projects were unified under an umbrella biomarker program, which might be of help to other research teams pursuing similar approaches.

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“…On the other hand, there have been recent studies on chronic neurological diseases using cell‐free DNA in cerebrospinal fluid (CSF) samples . There was a study that analyzed serial nuclear and mitochondrial DNA levels in plasma and CSF for patients with subarachnoid hemorrhage .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of neutrophil extracellular traps as the circulating marker for patients with acute coronary syndrome and acute ischemic stroke

Lim

Jeong

et al. 2020

Clinical Laboratory Analysis

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Introduction:Neutrophil extracellular traps (NETs) are known to be induced by various factors. In this study, we tried to identify circulating levels of NETs in patients with acute coronary syndrome (ACS) and acute ischemic stroke (AIS) and to confirm its suitability as a new circulating marker in their detection. Methods:We prospectively enrolled 95 patients with a diagnosis of ACS (N = 37) or AIS (N = 58) in Dong-A University Hospital, Busan, Korea. The control group was selected from healthy adults (N = 25) who visited the hospital for health screening.Circulating levels of NETs were evaluated by measuring plasma concentrations of double-stranded DNA (dsDNA) and DNA-histone complex. Results:The concentrations of dsDNA were statistically higher in patients with ACS or AIS than those in the control group (both P < .001). In the univariable and multivariable analyses, statistically significant risk factors were troponin I (TnI) level and dsDNA concentration in the ACS group (P = .046 and P = .015, respectively) and only dsDNA concentration in the AIS group (P = .002). In the receiver operating characteristic curve analyses, the area under the curve values for TnI level and dsDNA concentration in the ACS group were 0.878 and 0.968, respectively, and the value for dsDNA concentration in the AIS group was 0.859.

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Cerebrospinal fluid mitochondrial DNA in the Alzheimer's disease continuum

Cited by 29 publications

References 23 publications

Post-mortem ventricular cerebrospinal fluid cell-free-mtDNA in neurodegenerative disease

Post-mortem ventricular cerebrospinal fluid cell-free-mtDNA in neurodegenerative disease

The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: A data set for biomarker discovery and validation in neurodegenerative disorders

Evaluation of neutrophil extracellular traps as the circulating marker for patients with acute coronary syndrome and acute ischemic stroke

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