Towards a unified protocol for handling of CSF before β-amyloid measurements.


BACKGROUND:Widespread implementation of Alzheimer's disease biomarkers in routine clinical practice requires the establishment of standard operating procedures for pre-analytical handling of cerebrospinal fluid (CSF). METHODS:Here, CSF collection and storage protocols were optimized for measurements of β-amyloid (Aβ). We investigated the effects of (1) storage temperature, (2) storage time, (3) centrifugation, (4) sample mixing, (5) blood contamination, and (6) collection gradient on CSF levels of Aβ. For each study participant, we used fresh CSF directly collected into a protein low binding (LoB) tube that was analyzed within hours after lumbar puncture (LP) as standard of truth. Aβ42 and Aβ40 were measured in de-identified CSF samples using EUROIMMUN and Mesoscale discovery assays. RESULTS:CSF Aβ42 and Aβ40 were stable for at least 72 h at room temperature (RT), 1 week at 4 °C, and 2 weeks at - 20 °C and - 80 °C. Centrifugation of non-blood-contaminated CSF or mixing of samples before the analysis did not affect Aβ levels. Addition of 0.1-10% blood to CSF that was stored at RT without centrifugation led to a dose- and time-dependent decrease in Aβ42 and Aβ40, while Aβ42/Aβ40 did not change. The effects of blood contamination were mitigated by centrifugation and/or storage at 4 °C or - 20 °C. Aβ levels did not differ between the first to fourth 5-ml portions of CSF. CONCLUSIONS:CSF can be stored for up to 72 h at RT, 1 week at 4 °C, or at least 2 weeks at either - 20 °C or - 80 °C before Aβ measurements. Centrifugation of fresh non-blood-contaminated CSF after LP, or mixing before analysis, is not required. In case of visible blood contamination, centrifugation and storage at 4 °C or - 20 °C is recommended. After discarding the first 2 ml, any portion of up to 20 ml of CSF is suitable for Aβ analysis. These findings will be important for the development of a clinical routine protocol for pre-analytical handling of CSF.


Alzheimers Res Ther


Janelidze S,Stomrud E,Brix B,Hansson O




Has Abstract


2019-07-19 00:00:00












  • Active immunotherapy options for Alzheimer's disease.

    abstract::Alzheimer's disease (AD) is the most common cause of dementia and a major contributor to disability and dependency among older people. AD pathogenesis is associated with the accumulation of amyloid-beta protein (Aβ) and/or hyperphosphorylated tau protein in the brain. At present, current therapies provide temporary sy...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章,评审


    authors: Winblad B,Graf A,Riviere ME,Andreasen N,Ryan JM

    更新日期:2014-01-30 00:00:00

  • Systemic and central nervous system metabolic alterations in Alzheimer's disease.

    abstract:BACKGROUND:Metabolic alterations, related to cerebral glucose metabolism, brain insulin resistance, and age-induced mitochondrial dysfunction, play an important role in Alzheimer's disease (AD) on both the systemic and central nervous system level. To study the extent and significance of these alterations in AD, quanti...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: van der Velpen V,Teav T,Gallart-Ayala H,Mehl F,Konz I,Clark C,Oikonomidi A,Peyratout G,Henry H,Delorenzi M,Ivanisevic J,Popp J

    更新日期:2019-11-28 00:00:00

  • Risk of head and traumatic brain injuries associated with antidepressant use among community-dwelling persons with Alzheimer's disease: a nationwide matched cohort study.

    abstract:BACKGROUND:Antidepressant use has been associated with an increased risk of falling, but no studies have been conducted on whether antidepressant use is associated with an increased risk of head injuries which often result from falling among older persons. The objective of this study was to investigate the risk of head...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Taipale H,Koponen M,Tanskanen A,Lavikainen P,Sund R,Tiihonen J,Hartikainen S,Tolppanen AM

    更新日期:2017-08-01 00:00:00

  • Cognitive training and brain stimulation in prodromal Alzheimer's disease (AD-Stim)-study protocol for a double-blind randomized controlled phase IIb (monocenter) trial.

    abstract:BACKGROUND:Given the growing older population worldwide, and the associated increase in age-related diseases, such as Alzheimer's disease (AD), investigating non-invasive methods to ameliorate or even prevent cognitive decline in prodromal AD is highly relevant. Previous studies suggest transcranial direct current stim...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Thams F,Kuzmina A,Backhaus M,Li SC,Grittner U,Antonenko D,Flöel A

    更新日期:2020-11-07 00:00:00

  • A language-based sum score for the course and therapeutic intervention in primary progressive aphasia.

    abstract:BACKGROUND:With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the lit...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Semler E,Anderl-Straub S,Uttner I,Diehl-Schmid J,Danek A,Einsiedler B,Fassbender K,Fliessbach K,Huppertz HJ,Jahn H,Kornhuber J,Landwehrmeyer B,Lauer M,Muche R,Prudlo J,Schneider A,Schroeter ML,Ludolph AC,Otto M,FTLD

    更新日期:2018-04-25 00:00:00

  • In vivo quantification of neurofibrillary tangles with [18F]MK-6240.

    abstract:BACKGROUND:Imaging agents capable of quantifying the brain's tau aggregates will allow a more precise staging of Alzheimer's disease (AD). The aim of the present study was to examine the in vitro properties as well as the in vivo kinetics, using gold standard methods, of the novel positron emission tomography (PET) tau...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Pascoal TA,Shin M,Kang MS,Chamoun M,Chartrand D,Mathotaarachchi S,Bennacef I,Therriault J,Ng KP,Hopewell R,Bouhachi R,Hsiao HH,Benedet AL,Soucy JP,Massarweh G,Gauthier S,Rosa-Neto P

    更新日期:2018-07-31 00:00:00

  • APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain.

    abstract:BACKGROUND:The application of advanced sequencing technologies and improved mass-spectrometry platforms revealed significant changes in gene expression and lipids in Alzheimer's disease (AD) brain. The results so far have prompted further research using "multi-omics" approaches. These approaches become particularly rel...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Lefterov I,Wolfe CM,Fitz NF,Nam KN,Letronne F,Biedrzycki RJ,Kofler J,Han X,Wang J,Schug J,Koldamova R

    更新日期:2019-12-30 00:00:00

  • Changes in the neurochemistry of athletes with repetitive brain trauma: preliminary results using localized correlated spectroscopy.

    abstract:INTRODUCTION:The goal was to identify which neurochemicals differ in professional athletes with repetitive brain trauma (RBT) when compared to healthy controls using a relatively new technology, in vivo Localized COrrelated SpectroscopY (L-COSY). METHODS:To achieve this, L-COSY was used to examine five former professi...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Lin AP,Ramadan S,Stern RA,Box HC,Nowinski CJ,Ross BD,Mountford CE

    更新日期:2015-03-15 00:00:00

  • Preanalytical approaches to improve recovery of amyloid-β peptides from CSF as measured by immunological or mass spectrometry-based assays.

    abstract:BACKGROUND:Amyloid-β 1-42 (Aβ1-42) peptide is a well-established cerebrospinal fluid (CSF) biomarker for Alzheimer's disease (AD). Reduced levels of Aβ1-42 are indicative of AD, but significant variation in the absolute concentrations of this analyte has been described for both healthy and diseased populations. Preanal...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Schauer SP,Mylott WR Jr,Yuan M,Jenkins RG,Rodney Mathews W,Honigberg LA,Wildsmith KR

    更新日期:2018-11-28 00:00:00

  • The effects of different familial Alzheimer's disease mutations on APP processing in vivo.

    abstract:BACKGROUND:Disturbed amyloid precursor protein (APP) processing is considered to be central to the pathogenesis of Alzheimer's disease (AD). The autosomal dominant form of the disease, familial AD (FAD), may serve as a model for the sporadic form of AD. In FAD the diagnosis of AD is reliable and presymptomatic individu...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Thordardottir S,Kinhult Ståhlbom A,Almkvist O,Thonberg H,Eriksdotter M,Zetterberg H,Blennow K,Graff C

    更新日期:2017-02-16 00:00:00

  • Cognitive and affective theory of mind in dementia with Lewy bodies and Alzheimer's disease.

    abstract:BACKGROUND:Theory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Heitz C,Noblet V,Phillipps C,Cretin B,Vogt N,Philippi N,Kemp J,de Petigny X,Bilger M,Demuynck C,Martin-Hunyadi C,Armspach JP,Blanc F

    更新日期:2016-03-16 00:00:00

  • Total testosterone and neuropsychiatric symptoms in elderly men with Alzheimer's disease.

    abstract:INTRODUCTION:There has been a significant increase in the use of testosterone in aging men, but little investigation into its impact on men with Alzheimer's disease (AD). The findings of the few studies that have been done are inconsistent. In the present study, we investigated the relationship between total testostero...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Hall JR,Wiechmann AR,Cunningham RL,Johnson LA,Edwards M,Barber RC,Singh M,Winter S,O'Bryant SE,Texas Alzheimer’s Research and Care Consortium.

    更新日期:2015-05-01 00:00:00

  • The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer's disease.

    abstract:INTRODUCTION:Depression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies betwe...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Vermeiren Y,Van Dam D,Aerts T,Engelborghs S,Martin JJ,De Deyn PP

    更新日期:2015-02-11 00:00:00

  • Subjective cognitive decline and subsequent dementia: a nationwide cohort study of 579,710 people aged 66 years in South Korea.

    abstract:BACKGROUND:Subjective cognitive decline (SCD) is a potential risk factor for dementia. We aimed to investigate the association between SCD and subsequent dementia in a nationwide population-based cohort in South Korea. METHODS:This cohort included 579,710 66-year-old adults who were followed for a total of 3,870,293 p...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Lee YC,Kang JM,Lee H,Kim K,Kim S,Yu TY,Lee EM,Kim CT,Kim DK,Lewis M,Won HH,Jessen F,Myung W

    更新日期:2020-05-06 00:00:00

  • The relationship of weight change trajectory with medial temporal lobe atrophy in patients with mild Alzheimer's disease: results from a cohort study.

    abstract:INTRODUCTION:Weight loss has been described in 20% to 45% of patients with Alzheimer's disease (AD) and has been associated with adverse outcomes. Various mechanisms for weight loss in AD patients have been proposed, though none has been proven. This study aimed to elucidate a mechanism of weight loss in AD patients by...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Droogsma E,van Asselt D,Bieze H,Veeger N,De Deyn PP

    更新日期:2015-04-06 00:00:00

  • Alzheimer's disease drug-development pipeline: few candidates, frequent failures.

    abstract:INTRODUCTION:Alzheimer's disease (AD) is increasing in frequency as the global population ages. Five drugs are approved for treatment of AD, including four cholinesterase inhibitors and an N-methyl-D-aspartate (NMDA)-receptor antagonist. We have an urgent need to find new therapies for AD. METHODS:We examined Clinical...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Cummings JL,Morstorf T,Zhong K

    更新日期:2014-07-03 00:00:00

  • Effects of functional tasks exercise on cognitive functions of older adults with mild cognitive impairment: a randomized controlled pilot trial.

    abstract:BACKGROUND:Dementia has been presenting an imminent public health challenge worldwide. Studies have shown a combination of cognitive and physical trainings may have synergistic value for improving cognitive functions. Daily functional tasks are innately cognitive demanding and involve components found in common exercis...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章,随机对照试验


    authors: Law LLF,Mok VCT,Yau MMK

    更新日期:2019-12-04 00:00:00

  • Disclosure of amyloid positron emission tomography results to individuals without dementia: a systematic review.

    abstract:BACKGROUND:Disclosure of amyloid positron emission tomography (PET) results to individuals without dementia has become standard practice in secondary prevention trials and also increasingly occurs in clinical practice. However, this is controversial given the current lack of understanding of the predictive value of a P...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: de Wilde A,van Buchem MM,Otten RHJ,Bouwman F,Stephens A,Barkhof F,Scheltens P,van der Flier WM

    更新日期:2018-07-28 00:00:00

  • Older patients are still under-represented in clinical trials of Alzheimer's disease.

    abstract:BACKGROUND:The age gap between participants in trials and patients who could benefit from the drugs studied has been widely documented across different clinical areas. Patients with dementia included in clinical research are systematically younger than those in the general population. We examined the age gap between pa...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章,评审


    authors: Banzi R,Camaioni P,Tettamanti M,Bertele' V,Lucca U

    更新日期:2016-08-12 00:00:00

  • Does a prion-like mechanism play a major role in the apparent spread of α-synuclein pathology?

    abstract::Parkinson's disease, the most common movement disorder, results in an insidious reduction for patients in quality of life and ability to function. A hallmark of Parkinson's disease is the brain accumulation of neuronal cytoplasmic inclusions comprised of the protein α-synuclein. The presence of α-synuclein brain aggre...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章,评审


    authors: Sacino AN,Giasson BI

    更新日期:2012-12-17 00:00:00

  • A Quick Test of cognitive speed is sensitive in detecting early treatment response in Alzheimer's disease.

    abstract:INTRODUCTION:There is a great need for quick tests that identify treatment response in Alzheimer's disease (AD) to determine who benefits from the treatment. In this study, A Quick Test of cognitive speed (AQT) was compared with the mini-mental state examination (MMSE) in the evaluation of treatment outcome in AD. MET...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Palmqvist S,Minthon L,Wattmo C,Londos E,Hansson O

    更新日期:2010-10-15 00:00:00

  • Cerebrospinal fluid A beta 1-40 peptides increase in Alzheimer's disease and are highly correlated with phospho-tau in control individuals.

    abstract:BACKGROUND:Amyloid pathology, which is one of the characteristics of Alzheimer's disease (AD), results from altered metabolism of the beta-amyloid (Aβ) peptide in terms of synthesis, clearance, or aggregation. A decrease in cerebrospinal fluid (CSF) level Aβ1-42 is evident in AD, and the CSF ratio Aβ42/Aβ40 has recentl...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Lehmann S,Dumurgier J,Ayrignac X,Marelli C,Alcolea D,Ormaechea JF,Thouvenot E,Delaby C,Hirtz C,Vialaret J,Ginestet N,Bouaziz-Amar E,Laplanche JL,Labauge P,Paquet C,Lleo A,Gabelle A,Alzheimer’s Disease Neuroimaging Initi

    更新日期:2020-10-02 00:00:00

  • Analysis of brain region-specific co-expression networks reveals clustering of established and novel genes associated with Alzheimer disease.

    abstract:BACKGROUND:Identifying and understanding the functional role of genetic risk factors for Alzheimer disease (AD) has been complicated by the variability of genetic influences across brain regions and confounding with age-related neurodegeneration. METHODS:A gene co-expression network was constructed using data obtained...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Lancour D,Dupuis J,Mayeux R,Haines JL,Pericak-Vance MA,Schellenberg GC,Crovella M,Farrer LA,Kasif S

    更新日期:2020-09-02 00:00:00

  • Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative.

    abstract:BACKGROUND:Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive ...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Marquié M,Valero S,Castilla-Marti M,Martínez J,Rodríguez-Gómez O,Sanabria Á,Tartari JP,Monté-Rubio GC,Sotolongo-Grau O,Alegret M,Pérez-Cordón A,Roberto N,de Rojas I,Moreno-Grau S,Montrreal L,Hernández I,Rosende-Roca M,M

    更新日期:2020-03-31 00:00:00

  • Biomarkers in biological fluids for dementia with Lewy bodies.

    abstract::Dementia with Lewy bodies (DLB) has become the second most common neurodegenerative dementia due to demographic ageing. Differential diagnosis is still troublesome especially in early stages of the disease, since there is a great clinical and neuropathological overlap primarily with Alzheimer's disease and Parkinson's...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章,评审


    authors: Schade S,Mollenhauer B

    更新日期:2014-10-16 00:00:00

  • ADAM10 plasma levels predict worsening in cognition of older adults: a 3-year follow-up study.

    abstract:BACKGROUND:Blood-based biomarkers for Alzheimer's disease (AD) are highly needed in clinic practice. So far, the gold standards for AD diagnosis are brain neuroimaging and beta-amyloid peptide, total tau, and phosphorylated tau in cerebrospinal fluid (CSF); however, they are not attractive for large-scale screening. Bl...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Oliveira Monteiro MPA,Salheb Oliveira DSM,Manzine PR,Crispim Nascimento CM,Dos Santos Orlandi AA,de Oliveira Gomes GA,Dos Santos Orlandi F,Zazzetta MS,Pott-Junior H,Cominetti MR

    更新日期:2021-01-08 00:00:00

  • Health-related quality of life in people with predementia Alzheimer's disease, mild cognitive impairment or dementia measured with preference-based instruments: a systematic literature review.

    abstract:BACKGROUND:Obtaining reliable estimates of the health-related quality of life (HR-QoL) of people with predementia Alzheimer's disease [AD] (preclinical or prodromal AD), mild cognitive impairment (MCI) and dementia is essential for economic evaluations of related health interventions. AIMS:To provide an overview of wh...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章,评审


    authors: Landeiro F,Mughal S,Walsh K,Nye E,Morton J,Williams H,Ghinai I,Castro Y,Leal J,Roberts N,Wace H,Handels R,Lecomte P,Gustavsson A,Roncancio-Diaz E,Belger M,Jhuti GS,Bouvy JC,Potashman MH,Tockhorn-Heidenreich A,Gray

    更新日期:2020-11-18 00:00:00

  • Increased Aβ42-α7-like nicotinic acetylcholine receptor complex level in lymphocytes is associated with apolipoprotein E4-driven Alzheimer's disease pathogenesis.

    abstract:BACKGROUND:The apolipoprotein E ε4 (APOE4) genotype is a prominent late-onset Alzheimer's disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation. METHODS:Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Wang HY,Trocmé-Thibierge C,Stucky A,Shah SM,Kvasic J,Khan A,Morain P,Guignot I,Bouguen E,Deschet K,Pueyo M,Mocaer E,Ousset PJ,Vellas B,Kiyasova V

    更新日期:2017-07-27 00:00:00

  • Assessment of kallikrein 6 as a cross-sectional and longitudinal biomarker for Alzheimer's disease.

    abstract:BACKGROUND:Kallikrein 6 (KLK6) is known to be an age-related protease expressed at high levels in the central nervous system. It was previously shown to be involved in proteolysis of extracellular proteins implicated in neurodegenerative diseases such as Alzheimer's disease (AD), prompting validation of KLK6 as a poten...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Patra K,Soosaipillai A,Sando SB,Lauridsen C,Berge G,Møller I,Grøntvedt GR,Bråthen G,Begcevic I,Moussaud S,Minthon L,Hansson O,Diamandis EP,White LR,Nielsen HM

    更新日期:2018-01-29 00:00:00

  • Diffusion kurtosis imaging allows the early detection and longitudinal follow-up of amyloid-β-induced pathology.

    abstract:BACKGROUND:Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly population. In this study, we used the APP/PS1 transgenic mouse model to explore the feasibility of using diffusion kurtosis imaging (DKI) as a tool for the early detection of microstruct...

    journal_title:Alzheimer's research & therapy

    pub_type: 杂志文章


    authors: Praet J,Manyakov NV,Muchene L,Mai Z,Terzopoulos V,de Backer S,Torremans A,Guns PJ,Van De Casteele T,Bottelbergs A,Van Broeck B,Sijbers J,Smeets D,Shkedy Z,Bijnens L,Pemberton DJ,Schmidt ME,Van der Linden A,Verhoye M

    更新日期:2018-01-09 00:00:00