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cerebrospinal fluid neurogranin as a new player in prion disease diagnosis and prognosis

Neural Regeneration Research 2020年第5期15卷 861-862页

作者： Anna Villar-Piqué Inga Zerr Franc Llorens Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) Institute Carlos IIIMinistry of HealthHospitalet de LlobregatSpain Bellvitge Biomedical Research Institute (IDIBELL) Hospitalet de LlobregatSpain Department of Neurology Clinical Dementia Center and National Reference Center for CJD SurveillanceUniversity Medical SchoolGotingenGermany German Center for Neurodegenerative Diseases (DZNE) GotingenGermany

Neurogranin (Ng) and its role as Alzheimer’s disease (AD) biomarker: Ng is a calmodulin-binding protein mainly expressed in cerebral structures such as the cortex,hippocampus and striatum.It is mainly located in the dendritic processes,particularly in post-synaptic compartments,but also in the cytosolic compartment,being likely involved in the regulation of the intracellular calcium-calmodulin signaling pathway (Represa et al.,1990).In the last decade,a plethora of studies have demonstrated that cerebrospinal fluid (CSF) Ng is increased in AD patients and in individuals with an ADlike CSF profile (Kester et al.,2015a).This increase seems to be disease-specific because other neurodegenerative conditions including frontotemporal dementia,Lewy body dementia,Parkinson’s disease,progressive supranuclear palsy,multiple system atrophy or Huntington’s disease,present CSF Ng concentrations similar to controls (Wellington et al.,2016).Ng levels in CSF appear to be elevated in mild cognitive impairment (MCI)-affected individuals who progress to AD and are highly related to memory and cognitive function (Kester et al.,2015a;Tarawneh et al.,2016),which indicates that this protein may serve as an early AD biomarker with diagnostic utility in pre-dementia disease stages,and with prognostic utility to predict cognitive decline and MCI-to-AD conversion.

关键词： Represa cerebrospinal fluid multiple system

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The characteristics of cerebrospinal fluid tumor microenvironment in a patient with leptomeningeal metastases from cancer of unknown primary

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Genes & Diseases 2024年第3期11卷 39-42页

作者： Haoyu Ruan Zhe Wang Xuemei Tang Qiong Zhan Kun Chen Lu Gao Ming Guan Department of Laboratory Medicine Huashan HospitalFudan UniversityShanghai 200040China Department of Laboratory Medicine The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Physiology Naval Medical UniversityShanghai 200433China Department of Oncology Huashan HospitalFudan UniversityShanghai 200040China

Cancer of unknown primary(CUP)is a rare disease characterized by metastases in which the primary tumor is of unknown origin.The cerebrospinal fluid(CSF)tumor microenvironment of CUP is still unknown.A Chinese male was diagnosed with leptomeningeal metastases from CUP(CUP-LM)based on the following medical examination results:partial leptomeningeal enhancement by brain magnetic resonance imaging,few malignant cells of diverse morphology in CSF,and no abnormalities or lymphadenopathy by systemic examination.

关键词： metastases cerebrospinal fluid

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Alzheimer’s disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling

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The Innovation 2024年第1期5卷 118-126页

作者： Qing-Qing Tao Xue Cai Yan-Yan Xue Weigang Ge Liang Yue Xiao-Yan Li Rong-Rong Lin Guo-Ping Peng Wenhao Jiang Sainan Li Kun-Mu Zheng Bin Jiang Jian-Ping Jia Tiannan Guo Zhi-Ying Wu Department of Neurology and Research Center of Neurology in the Second Affiliated Hospital and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of MedicineHangzhou 310009China Liangzhu Laboratory Zhejiang UniversityHangzhou 311100China Westlake Laboratory of Life Sciences and Biomedicine Key Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake UniversityHangzhou 310024China Institute of Basic Medical Sciences Westlake Institute for Advanced StudyHangzho 310024China Department of Neurology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Neurology First Affiliated HospitalSchool of MedicineXiamen UniversityXiamen 361009China Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijing 100053China MOE Frontier Science Center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China

Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers.More ADspecific early diagnostic and disease staging biomarkers are needed.In this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 participants.Candidate biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 participants.We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,respectively.In the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,respectively.Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,respectively.The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases.Moreover,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD stages.Our findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.

关键词： cerebrospinal Alzheimer fluid

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Neuron-specific enolase in cerebrospinal fluid as a biomarker of brain damage in infants with hypoxic-ischemic encephalopathy

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Neural Regeneration Research 2022年第2期17卷 318-319页

作者： Alfredo Garcia-Alix Juan Arnaez Neonatal Neurology NeNe FoundationSpain Neonatology Complejo Universitario de BurgosBurgosSpain

Neonatal encephalopathy resulting from an asphyxial episode occurring perinatally is a major cause of death and of permanent neurological disabilities worldwide. Therapeutic hypothermia(TH) started within 6 hours of life and maintained for 72 hours is now well established as standard treatment for infants with moderate-to-severe hypoxicischemic encephalopathy(HIE).

关键词： damage Neuron death cerebrospinal

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cerebrospinal Fluid Biomarkers in Dementia Patients with Cerebral Amyloid Angiopathy

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Chinese Medical Sciences Journal 2015年第3期30卷 170-173页

作者： Yan-feng Li Fang-fang Ge Yong Zhang Hui You Zhen-xin Zhang Department of Neurology Department of Radiology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100730 China

Objective To study the changes of biomarkers in cerebrospinal fluid(CSF) in cerebral amyloid angiopathy(CAA) dementia and Alzheimer's disease.Methods Levels of amyloid protein β(Aβ42,Aβ40) and phosphorylated Tau-protein(P-tau) in CSF and ratio of Aβ42/Aβ40 were tested in 5 cases with CAA dementia and 20 cases with Alzheimer's disease collected at Peking Union Medical College Hospital from December 2001 to March 2011.Results The levels of Aβ42,Aβ40,and P-tau in CSF and ratio of Aβ42/Aβ40 were(660.4±265.2) ng/L,(7111.0±1033.4) ng/L,(71.8±51.5) ng/L,and 0.077±0.033,respectively in CAA dementia and(663.6±365.6) ng/L,(5115.0±2931.1) ng/L,(47.7±38.8) ng/L,and 0.192±0.140,respectively in Alzheimer's disease patients.There were no statistically significant differences between CAA dementia and Alzheimer's disease in terms of these CSF biomarkers(all P>0.05).Conclusion Measurements of CSF biomarkers may not be helpful in differential diagnosis of CAA and Alzheimer's disease.

关键词： cerebral amyloid angiopathy Alzheimer's disease cerebrospinal fluid biomarker

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Serum and cerebrospinal fluid tau protein level as biomarkers for evaluating acute spinal cord injury severity and motor function outcome

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Neural Regeneration Research 2019年第5期14卷 896-902页

作者： Ying Tang Hong-Liang Liu Ling-Xia Min Hao-Shi Yuan Lei Guo Peng-Bo Han Yu-Xin Lu Jian-Feng Zhong Dong-Lin Wang Key Laboratory of Biorheological Science and Technology Ministry of Education (Chongqing University) Chongqing University Cancer Hospital Department of Rehabilitation Southwest Hospital Third Military Medical University Department of Spine Surgery Second Affiliated Hospital of Xi'an Medical University Department of Orthopedics Chinese PLA Beijing Army General Hospital

Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm(mild), 25 mm(moderate) and 50 mm(severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups(both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days(serum: r =-0.94; cerebrospinal fluid: r =-0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.

关键词： nerve regeneration spinal cord injury tau injury severity outcome cerebrospinal fluid serum biomarker Basso,Beattie,and Bresnahan locomotor rating scale neural regeneration

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Validation of Angiostrongylus cantonensis combined with herpes simplex virus type 1 in cerebrospinal fluid by next-generation sequencing

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Chinese Medical Journal 2020年第2期133卷 247-249页

作者： Yong-Fang Zhang Sheng-Nan Wang Dong-Mei Wang Kai-Bin Huang Ya-Fang Hu Department of Neurology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

To the Editor:Angiostrongylus cantonensis is one of the major causes of eosinophilic meningitis/meningoencephalitis,due to eating raw or undercooked paratenic or intermediate hosts like mollusks.Here,we described a case of combined infection of A.cantonensis and herpes simplex virus type 1(HSV-1)based on the results of next-generation sequencing(NGS).

关键词： encephalitis cerebrospinal fluid

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Osmotic pressure of serum and cerebrospinal fluid in patients with suspected neurological conditions

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Neural Regeneration Research 2020年第5期15卷 944-947页

作者： Tetsuya Akaishi Toshiyuki Takahashi Ichiro Nakashima Michiaki Abe Masashi Aoki Tadashi Ishii Department of Education and Support for Regional Medicine Tohoku University HospitalSendaiJapan Department of Neurology Tohoku University Graduate School of MedicineSendaiJapan Department of Neurology National Hospital Organization Yonezawa National HospitalYonezawaJapan Department of Neurology Tohoku Medical and Pharmaceutical UniversitySendaiJapan

Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic pressure gradient may be one of the driving forces of this bulk flow.However,osmotic pressure- related factors have not been studied until now.In this prospective observational study,to elucidate the relationship between osmolality (mOsm/kg) in the serum and that in the cerebrospinal fluid (CSF),we simultaneously measured the serum and CSF osmolality of 179 subjects with suspected neurological conditions.Serum osmolality was 283.6 ± 6.5 mOsm/kg and CSF osmolality was 289.5 ± 6.6 mOsm/kg.Because the specific gravity of serum and CSF is known to be 1.024–1.028 and 1.004–1.007,respectively,the estimated average of osmolarity (mOsm/L) in the serum and CSF covered exactly the same range (i.e.,290.5–291.5 mOsm/L).There was strong correlation between CSF osmolality and serum osmolality,but the difference in osmolality between serum and CSF was not correlated with serum osmolality,serum electrolyte levels,protein levels,or quotient of albumin.In conclusion,CSF osmolarity was suggested to be equal to serum osmolarity.Osmolarity is not one of the driving forces of this bulk flow.Other factors such as hydrostatic pressure gradient should be used to explain the mechanism of bulk flow in the brain parenchyma.This study was approved by the Institutional Review Board of the Tohoku University Hospital (approval No.IRB No.2015-1-257) on July 29,2015.

关键词： brain parenchyma bulk flow cerebrospinal fluid hydrostatic pressure interstitial fluid osmolarity osmotic pressure

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Young cerebrospinal fluid contains key rejuvenating factors

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Life Metabolism 2022年第2期1卷 103-104页

作者： Dongming Zhang Dongsheng Cai Department of Molecular Pharmacology Albert Einstein College of MedicineBronxNYUSA

In a recent study published in Nature,Iram et al.reported that treatment with young cerebrospinal fluid can play a rejuvenating function in older mice by promoting the proliferation and differentiation of oligodendroc... 详细信息

关键词： cerebrospinal fluid

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cerebrospinal fluid and blood biomarkers in Alzheimer’s disease

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World Journal of Psychiatry 2011年第1期1卷 8-18页

作者： Christian Humpel Tanja Hochstrasser Laboratory for Psychiatry and Experimental Alzheimer’s Research Department of Psychiatry and PsychotherapyInnsbruck Medical University6020 InnsbruckAustria

Due to an ever aging society and growing prevalence of Alzheimer’s disease(AD),the challenge to meet social and health care system needs will become increasingly difficult.Unfortunately,a definite ante mortem diagnosis is not possible.Thus,an early diagnosis and identification of AD patients is critical for promising,early pharmacological interventions as well as addressing health care needs.The most advanced and most reliable markers areβ-amyloid,total tau and phosphorylated tau in cerebrospinal fluid(CSF).In blood,no single biomarker has been identified despite an intense search over the last decade.The most promising approaches consist of a combination of several bloodbased markers increasing the reliability,sensitivity and specificity of the AD diagnosis.However,contradictory data make standardized testing methods in longitudinal and multi-center studies extremely difficult.In this review,we summarize a range of the most promising CSF and blood biomarkers for diagnosing AD.

关键词： Alzheimer’s disease Biomarker Blood cerebrospinal fluid Dementia Plasma

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