Raman Spectroscopy to Diagnose Alzheimer's Disease and Dementia with Lewy Bodies in Blood.

Accurate identification of Alzheimer's disease (AD) is still of major clinical importance considering the current lack of noninvasive and low-cost diagnostic approaches. Detection of early stage AD is particularly desirable as it would allow early intervention or recruitment of patients into clinical trials. There is also an unmet need for discrimination of AD from dementia with Lewy bodies (DLB), as many cases of the latter are misdiagnosed as AD. Biomarkers based on a simple blood test would be useful in research and clinical practice. Raman spectroscopy has been implemented to analyze blood plasma of a cohort that consisted of early stage AD, late-stage AD, DLB, and healthy controls. Classification algorithms achieved high accuracy for the different groups: early stage AD vs healthy with 84% sensitivity, 86% specificity; late-stage AD vs healthy with 84% sensitivity, 77% specificity; DLB vs healthy with 83% sensitivity, 87% specificity; early-stage AD vs DLB with 81% sensitivity, 88% specificity; late-stage AD vs DLB with 90% sensitivity, 93% specificity; and lastly, early-stage AD vs late-stage AD 66% sensitivity and 83% specificity. G-score values were also estimated between 74% and 91%, demonstrating that the overall performance of the classification model was satisfactory. The wavenumbers responsible for differentiation were assigned to important biomolecules, which can serve as a panel of biomarkers. These results suggest a cost-effective, blood-based test for neurodegeneration in dementias.

[1]  A. Nordberg,et al.  Tau PET imaging: present and future directions , 2017, Molecular Neurodegeneration.

[2]  Christian Humpel,et al.  Identifying and validating biomarkers for Alzheimer's disease , 2011, Trends in biotechnology.

[3]  M. Witter,et al.  Neuronal and Astrocytic Metabolism in a Transgenic Rat Model of Alzheimer's Disease , 2014, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[4]  Derick R. Peterson,et al.  Plasma phospholipids identify antecedent memory impairment in older adults , 2014, Nature Medicine.

[5]  T. J. Grabowski,et al.  FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease , 2008 .

[6]  N. Schork,et al.  Kinase mutations in human disease: interpreting genotype–phenotype relationships , 2010, Nature Reviews Genetics.

[7]  T. Beach A Review of Biomarkers for Neurodegenerative Disease: Will They Swing Us Across the Valley? , 2017, Neurology and Therapy.

[8]  S. Lovestone,et al.  Proteome-based plasma biomarkers for Alzheimer's disease. , 2006, Brain : a journal of neurology.

[9]  P. Martínez-Martín,et al.  Discrimination analysis of blood plasma associated with Alzheimer's disease using vibrational spectroscopy. , 2013, Journal of Alzheimer's disease : JAD.

[10]  S. Rehman,et al.  Raman Spectroscopy of Biological Tissues , 2007 .

[11]  D. Fuchs,et al.  Immune activation in patients with Alzheimer's disease is associated with high serum phenylalanine concentrations , 2013, Journal of the Neurological Sciences.

[12]  C. DeCarli,et al.  FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease. , 2007, Brain : a journal of neurology.

[13]  I. Lednev,et al.  Raman spectroscopy of blood serum for Alzheimer's disease diagnostics: specificity relative to other types of dementia , 2015, Journal of biophotonics.

[14]  Camilo L. M. Morais,et al.  Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood , 2017, Proceedings of the National Academy of Sciences.

[15]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[16]  J. Havelund,et al.  Biomarker Research in Parkinson’s Disease Using Metabolite Profiling , 2017, Metabolites.

[17]  K. S. Krishnan,et al.  A New Type of Secondary Radiation , 1928, Nature.

[18]  Alzheimer's Disease Neuroimaging Initiative Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease , 2017 .

[19]  Satoshi Minoshima,et al.  Alzheimer's disease versus dementia with Lewy bodies: Cerebral metabolic distinction with autopsy confirmation , 2001, Annals of neurology.

[20]  J. Griffin,et al.  Amino Acid Catabolism in Alzheimer's Disease Brain: Friend or Foe? , 2017, Oxidative medicine and cellular longevity.

[21]  K. Blennow,et al.  CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis , 2016, The Lancet Neurology.

[22]  E. Mori [Dementia with Lewy bodies]. , 2000, Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics.

[23]  Tianyue Yang,et al.  Discrimination of serum Raman spectroscopy between normal and colorectal cancer using selected parameters and regression-discriminant analysis. , 2012, Applied optics.

[24]  S. Patassini,et al.  Graded perturbations of metabolism in multiple regions of human brain in Alzheimer's disease: Snapshot of a pervasive metabolic disorder , 2016, Biochimica et biophysica acta.

[25]  Holly J. Butler,et al.  Using Raman spectroscopy to characterize biological materials , 2016, Nature Protocols.

[26]  W. Kukull,et al.  Theoretical Impact of Florbetapir (18F) Amyloid Imaging on Diagnosis of Alzheimer Dementia and Detection of Preclinical Cortical Amyloid , 2014, Journal of neuropathology and experimental neurology.

[27]  T. Hortobágyi,et al.  Accuracy of Clinical Diagnosis of Dementia with Lewy Bodies versus Neuropathology. , 2017, Journal of Alzheimer's disease : JAD.

[28]  J. L. Pichardo-Molina,et al.  Raman spectroscopy and multivariate analysis of serum samples from breast cancer patients , 2007, Lasers in Medical Science.

[29]  Krupal S. Parikh,et al.  Support Vector Machine – A Large Margin Classifier to Diagnose Skin Illnesses , 2016 .

[30]  Takashi Kasai,et al.  Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome , 2017, Molecular Neurodegeneration.

[31]  C. Krishna,et al.  Recurrence prediction in oral cancers: a serum Raman spectroscopy study. , 2015, The Analyst.

[32]  B. Boeve,et al.  Lewy body dementias , 2015, The Lancet.

[33]  Nick C Fox,et al.  Brain imaging in Alzheimer disease. , 2012, Cold Spring Harbor perspectives in medicine.

[34]  B. Winblad,et al.  Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer's disease neurofibrillary degeneration , 1998, Brain Research.

[35]  C. Jack,et al.  Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers , 2017, The Lancet Neurology.

[36]  Daniel R. Schonhaut,et al.  Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease. , 2016, Brain : a journal of neurology.

[37]  J. Gómez-Ariza,et al.  Metabolite profiling for the identification of altered metabolic pathways in Alzheimer's disease. , 2015, Journal of pharmaceutical and biomedical analysis.

[38]  D. Mann,et al.  Apolipoprotein E υ4 Allele Frequency in Vascular Dementia , 2006, Dementia and Geriatric Cognitive Disorders.

[39]  Francis L Martin,et al.  Extracting biological information with computational analysis of Fourier-transform infrared (FTIR) biospectroscopy datasets: current practices to future perspectives. , 2012, The Analyst.

[40]  Ronald C. Petersen,et al.  Identification of Altered Metabolic Pathways in Plasma and CSF in Mild Cognitive Impairment and Alzheimer’s Disease Using Metabolomics , 2013, PloS one.

[41]  Zongwei Cai,et al.  LC-MS-based urinary metabolite signatures in idiopathic Parkinson's disease. , 2015, Journal of proteome research.

[42]  W. Scheper,et al.  The unfolded protein response is activated in pretangle neurons in Alzheimer's disease hippocampus. , 2009, The American journal of pathology.

[43]  P. Mcgeer,et al.  Brain imaging in Alzheimer's disease. , 1986, British medical bulletin.

[44]  V. Mok,et al.  Comprehensive urinary metabolomic profiling and identification of potential noninvasive marker for idiopathic Parkinson’s disease , 2015, Scientific Reports.

[45]  Henrik Zetterberg,et al.  Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease , 2017, JAMA neurology.

[46]  Nick C Fox,et al.  The clinical use of structural MRI in Alzheimer disease , 2010, Nature Reviews Neurology.

[47]  Henrik Zetterberg,et al.  Plasma tau levels in Alzheimer's disease , 2013, Alzheimer's Research & Therapy.