Plasma biomarkers for mild cognitive impairment and Alzheimer's disease

Song, Fei; Poljak, Anne; Smythe, George A.; Sachdev, Perminder S.

doi:10.1016/j.brainresrev.2009.05.003

Cited by 160 publications

(135 citation statements)

References 344 publications

(483 reference statements)

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“…In addition, a growing focus is on biomarkers which enable detection of the disease in its early stages and will allow for preventative treatment (Song et al 2009). …”

Section: Alzheimer's Disease and The Urgent Need For Early Diagnosis mentioning

confidence: 99%

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

et al. 2012

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The use of induced pluripotent stem cells (iPSCs), whereby a patient's somatic cells can be reprogrammed to a pluripotent state by the forced expression of a defined set of transcription factors, has the potential to enable in vitro disease modelling and be used for drug discovery programs. Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that leads to a decline in memory and cognition. Fibroblasts were taken from AD patients (or non‐AD controls) and cultured under specific conditions to generate iPSCs which were then provided with growth factors to allow differentiation into neurons. While AD‐iPSCs were morphologically indistinguishable from control‐iPSCs, differentiated cells showed differing responses to both cellular stresses and neuroprotective drugs. Since these cells are derived from individual patients, the use of iPSCs has provided novel insights into disease pathogenesis, providing information on an individual's variations in the disease process and their cellular response to drugs.

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“…In addition, a growing focus is on biomarkers which enable detection of the disease in its early stages and will allow for preventative treatment (Song et al 2009). …”

Section: Alzheimer's Disease and The Urgent Need For Early Diagnosis mentioning

confidence: 99%

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

et al. 2012

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“…Potential neuroimaging techniques that can improve the accuracy to predict conversion to AD are considered as well as potential CSF, urine, blood and genetic biomarkers of AD (continuation). risk factor to MCI conversion to AD (45) associated with the risk of incident AD and dementia (51) and suitable in normal cognitive status conversion to MCI or AD (54,55) associated with higher risk of incident AD and dementia (51) lack of correlation between plasma Aβ levels and plasma homocysteine (50) and Aβ-42 levels in CSF and plasma (57,58) suitable to predict conversion to AD (sensitivity 80% and specificity 82%) (59) strongest correlations in MCI patients (60) strong correlations with oxidized lipoprotein receptor-related protein-1 (sLRP), CSF tau / Aβ-42 ratios and reductions in MMSE scores, risk of MCI and AD (81) correlation with cognitive function (62) useful tool to predict MCI conversion to AD (45,49,50,(63)(64)(65)70) reliable biochemical marker in early stages of AD and in the discrimination from other types of dementia (sensibility 87% and specificity 82%) (66) risk marker for AD in subjects with MCI (67) useful in prediction of incident impairment in asymptomatic individuals (68) predictive of cognitive decline and hippocampal volume loss (69) candidate biomarkers for AD and the predementia condition of MCI (73) related to familial AD (prevalence around 0,1%) (45) risk factor for AD (45) risk factor for sporadic AD (45) involved in familial AD and other neurodegenerative diseaes (80,81) (myo-inositol/creatine ratio) in the cortical area of right parietal lobe in MCI subjects predicted the conversion to AD with sensitivity 70% and specificity 85%.…”

Section: Challenges In the Discovery Of Potential Biomarkers In Alzhementioning

confidence: 99%

New perspectives in the search for reliable biomarkers in Alzheimer disease

2015

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-Background and Objectives:The search for accurate biomarkers in Alzheimer Disease (AD), on of the most devastating neurodegenerative diseases, remains essential to enable an early prognosis and diagnosis of the disease and to provide more efficient therapeutic strategies.A wide variety of potential biomarkers are has been identified by neuroimaging techniques and by the analysis of fluid samples, such as cerebrospinal fluid (CSF) or blood. Recently, a growing number of studies are focused on the discovery of reliable bloodbased biomarkers in blood, especially in the prodromal stage of AD, which can predict the conversion of asymptomatic cases to AD demented cases.In this review, the latest challenges in the search for accurate biomarkers of AD is revised, in particular, an update in blood-based biomarkers is described in depth.Conclusions: Finally, the close link among AD and other neurodegenerative diseases is discussed, mainly based on the last discovered mutation, the chromosome 9 open reading frame 72, C9ORF72. Challenges in the discovery of potential biomarkers in Alzheimer DiseaseTo date there are no effective therapies to preserve normal brain function in potential future Alzheimer's disease (AD) patients. The absence of reliable biomarkers to identify cognitive normal individuals that will become early-stage AD patients support this fact. Therefore, this overlap between demented and non-demented population has limited the diagnostic accuracy of the current known biomarkers for AD. Due to the fact that neurological processes that finally result in dementia are assumed to be actively long before the first symptoms appear, the availability of diagnostic biomarkers could make a preclinical diagnostic testing and an early treatment of AD possible.A great variety of biomarkers of AD has been described using different approaches (Table 1). As Figure 1 shows, different strategies can be studied along AD progression for a better understanding of the disease and to enable an accurate identification of potential AD biomarkers. Currently, the most studied methods to identify markers of mild cognitive impairment (MCI) and AD are neuroimaging and molecular techniques based on cerebrospinal fluid (CSF). A systematic search on PubMed and Scopus databases was performed to find the most relevant studies and review papers. The key words used for this purpose were: "Alzheimer's disease", "Mild Cognitive Impairment", "biomarkers", "blood", "neuroimaging" and "neurodegenerative diseases" in various combinations. The articles selected were published in English from 2004 to 2015.Neuroimaging is a non-invasive technique which monitors brain regions and allows the subsequent identification and quantification of diagnostic and candidate biomarkers of dementia progression 1 . Magnetic resonance imaging (MRI) is the most widely used neuroimaging technique to investigate brain changes and neurodegeneration. Several longitudinal studies using MRI have been conducted with positive results 2,3 . After followup assessments, th...

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“…In familial AD cases, total Aβ and Aβ1-42 plasma levels are elevated [79] . In sporadic AD, several cross-sectional studies report no significant difference in plasma Aβ concentrations in general compared to controls [79][80][81][82] . Unfortunately, longitudinal studies have shown high data variability.…”

Section: Aβ Peptidesmentioning

confidence: 99%

“…BACE cleaves APP and releases a large N-terminal fragment (sAPPβ). The membrane-anchored frag- [73,75] Decreased [65] β-amyloid (Aβ) Decreased [45,46] No difference [79][80][81][82] No difference [47] Aβ1- 40 No difference [24] No difference [83] Increased [84] Decreased [85] Aβ1- 42 Decreased [24] Increased [83] -Aβ1-42/Aβ1-40 ratio Decreased [48] No difference [83] Decreased [78,84,86] APP ratio --Decreased [90][91][92][93] Ubiquitin Increased [24] No difference [148] BACE1 Increased [67] --Cholesterol -Decreased [94,95] Increased [96][97][98] 24S-hydroxycholesterol Increased [102] No difference [103] Decreased [104] Homocysteine -Increased [106,107,109] Epidermal growth factor -Decreased [111] Decreased [93] Increased [112] Glial cell line-derived growth factor -Decreased [111] No difference …”

Section: Aβ1-42mentioning

confidence: 99%

Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease

Humpel

Hochstrasser²

2011

WJP

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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 are β-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.

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Plasma biomarkers for mild cognitive impairment and Alzheimer's disease

Abstract: A variety of potential plasma biomarkers for AD and MCI have been identified, however the findings need replication in longitudinal studies. This area of research promises to yield interesting results in the near future.

Cited by 160 publications

References 344 publications

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

New perspectives in the search for reliable biomarkers in Alzheimer disease

Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease

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