Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

@article{Perrin2011IdentificationAV,
  title={Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease},
  author={Richard J. Perrin and Rebecca Craig-Schapiro and James P. Malone and Aarti R. Shah and Petra E Gilmore and Alan E. Davis and Catherine M. Roe and Elaine Peskind and Ge Li and Douglas R. Galasko and Christopher M. Clark and Joseph F. Quinn and Jeffrey A. Kaye and John C. Morris and David M. Holtzman and Reid R. Townsend and Anne M. Fagan},
  journal={PLoS ONE},
  year={2011},
  volume={6}
}
Background Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the ‘preclinical’ stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we… 

Figures and Tables from this paper

Identification of longitudinally dynamic biomarkers in Alzheimer’s disease cerebrospinal fluid by targeted proteomics

A targeted-proteomic, multiple reaction monitoring (MRM) assay was developed for the absolute quantitation of 39 peptides corresponding to 30 proteins and four CSF markers demonstrated significant longitudinal change in AD: Amyloid precursor protein, Neuronal pentraxin receptor, NrCAM and Chromogranin A.

Upcoming candidate cerebrospinal fluid biomarkers of Alzheimer's disease.

The potential of several promising novel cerebrospinal fluid analytes are discussed, the next steps critical for advancement in the field are highlighted, and a prediction on how the field may evolve in 5-10 years is provided.

High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer’s Disease in Human Cerebrospinal Fluid

High resolution open discovery platform dMS was applied to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control) patients, and multiple markers were identified to be statistically significant in the cohort tested.

Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease

There is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals, and the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers.

Cerebrospinal fluid biomarkers of Alzheimer’s disease

The metabolism and diagnostic performance of the well-established core candidate cerebrospinal fluid biomarkers (β-amyloid, total tau, and hyperphosphorylated tau) are discussed and novel promising CSF biomarkers, especially those identified by proteomics, updated in the last five years are also extensively discussed.

Biomarkers for the Early Detection and Progression of Alzheimer’s Disease

The ultimate AD biomarker panel will likely involve the inclusion of novel CSF and blood biomarkers more precisely associated with confirmed pathophysiologic mechanisms to improve its reliability for detecting preclinical AD.

Fluid biomarkers in Alzheimer’s disease – current concepts

The core AD CSF biomarkers have high diagnostic accuracy both for AD with dementia and to predict incipient AD (MCI due to AD), which is important if disease-modifying treatment becomes available and if treatment will probably be most effective early in the disease.

Cerebrospinal fluid biomarkers for pathological processes in Alzheimer's disease

The CSF biomarkers total tau, phosphorylated-tau and the 42 amino acid isoform of amyloid beta reflect core elements of AD, that is, axonal degeneration, tangle disease and senile plaques, and provide high diagnostic accuracy in the discrimination of patients with AD as compared with cognitively normal controls.

Cerebrospinal fluid analysis in Alzheimer’s disease: technical issues and future developments

Unbiased systems biology-based diagnostic and prognostic models in AD will consist of relevant comprehensive panels of molecules and key branches of the disease-affected cellular neuronal network, which will more accurately and comprehensively reflect pathophysiology from the early asymPTomatic and presymptomatic to the final prodromal and symptomatic clinical stages in individual patients.

Fluid biomarkers in Alzheimer's disease - current

The core AD CSF biomarkers have high diagnostic accuracy both for AD with dementia and to predict incipient AD (MCI due to AD), which is important if disease-modifying treatment becomes available and if treatment will probably be most effective early in the disease.
...

References

SHOWING 1-10 OF 279 REFERENCES

A Novel Panel of Cerebrospinal Fluid Biomarkers for the Differential Diagnosis of Alzheimer’s Disease versus Normal Aging and Frontotemporal Dementia

A panel of cerebrospinal fluid protein markers was verified by a proteomics technology which may potentially improve the accuracy of the AD diagnosis.

Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer's disease and non-demented elderly subjects

The results suggest that multi-factor proteomic pattern analysis of the CSF may provide a means to diagnose and assess AD.

Novel panel of cerebrospinal fluid biomarkers for the prediction of progression to Alzheimer dementia in patients with mild cognitive impairment.

Proteomic profiling of cerebrospinal fluid provided a novel panel of 17 potential biomarkers for prediction of MCI progression to AD and the 5 identified biomarkers are relevant to the pathogenesis of AD and could help gain an understanding of the molecular pathways in which they may function.

Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment

A multi-prong analytical approach showed AD patients were best distinguished from non-AD cases by a combination of traditional AD biomarkers and novel multiplex biomarkers, which can improve the distinction between AD and non- AD cases by established biomarkers alone.

Proteome-based plasma biomarkers for Alzheimer's disease.

It is suggested that blood may be a rich source for biomarkers of Alzheimer's disease and that complement factor H, together with other proteins such as alpha-2M, May be a specific markers of this illness.

A panel of cerebrospinal fluid potential biomarkers for the diagnosis of Alzheimer's disease

The presence in the CSF of novel potential biomarkers for AD is demonstrated, which may be used for the diagnosis and perhaps the assessment of the severity and progression of the disease.

Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders.

The preliminary findings of iTRAQ suggest that a roster of proteins may be generated and developed into specific biomarkers that could eventually assist in clinical diagnosis and monitoring disease progression of AD, PD and DLB.

Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease.

Quantitative proteomics of CSF from AD patients compared to age-matched controls, as well as from other neurodegenerative diseases, will allow us to generate a roster of proteins that may serve as specific biomarker panels for AD and other geriatric dementias.
...