Comparative analyses of plasma amyloid-β levels in heterogeneous and monomerized states by interdigitated microelectrode sensor system

We compared levels of Aβ by self-standard in plasma using an interdigitated microelectrode sensor to detect Alzheimer disease. Detection of amyloid-β (Aβ) aggregates contributes to the diagnosis of Alzheimer disease (AD). Plasma Aβ is deemed a less invasive and more accessible hallmark of AD, as Aβ can penetrate blood-brain barriers. However, correlations between biofluidic Aβ concentrations and AD progression has been tenuous. Here, we introduce a diagnostic technique that compares the heterogeneous and the monomerized states of Aβ in plasma. We used a small molecule, EPPS [4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid], to dissociate aggregated Aβ into monomers to enhance quantification accuracy. Subsequently, Aβ levels of EPPS-treated plasma were compared to those of untreated samples to minimize inter- and intraindividual variations. The interdigitated microelectrode sensor system was used to measure plasma Aβ levels on a scale of 0.1 pg/ml. The implementation of this self-standard blood test resulted in substantial distinctions between patients with AD and individuals with normal cognition (NC), with selectivity and sensitivity over 90%.

[1]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[2]  E. Oguni,et al.  Amyloid β protein in plasma from patients with sporadic Alzheimer's disease , 1996, Journal of the Neurological Sciences.

[3]  D. Na,et al.  Normative data on the Korean version of the Boston Naming Test. , 1999, Journal of clinical and experimental neuropsychology.

[4]  K. Blennow,et al.  Cerebrospinal fluid beta-amyloid(1-42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. , 1999, Archives of neurology.

[5]  H. Wiśniewski,et al.  Plasma amyloid β‐peptide 1–42 and incipient Alzheimer's disease , 1999 .

[6]  P. Mehta,et al.  Amyloid β protein 1–40 and 1–42 levels in matched cerebrospinal fluid and plasma from patients with Alzheimer disease , 2001, Neuroscience Letters.

[7]  K. Janda,et al.  Biological tuning of synthetic tactics in solid-phase synthesis: application to A beta(1-42). , 2004, The Journal of organic chemistry.

[8]  R. Deane,et al.  RAGE (Yin) Versus LRP (Yang) Balance Regulates Alzheimer Amyloid &bgr;-Peptide Clearance Through Transport Across the Blood–Brain Barrier , 2004, Stroke.

[9]  K. Blennow,et al.  The Effect of Simvastatin Treatment on the Amyloid Precursor Protein and Brain Cholesterol Metabolism in Patients with Alzheimer’s Disease , 2005, Dementia and Geriatric Cognitive Disorders.

[10]  B. Reisberg,et al.  Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment , 2006, Neurobiology of Aging.

[11]  W. M. van der Flier,et al.  Longitudinal changes of CSF biomarkers in memory clinic patients , 2007, Neurology.

[12]  Paul Maruff,et al.  β-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease , 2007 .

[13]  R. Tibshirani,et al.  Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins , 2007, Nature Medicine.

[14]  Simon A. Moss,et al.  b -amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer’s disease , 2007 .

[15]  Y. Matsuo,et al.  Amyloid Oligomer Conformation in a Group of Natively Folded Proteins , 2008, PloS one.

[16]  Jeffrey A. James,et al.  Frequent amyloid deposition without significant cognitive impairment among the elderly. , 2008, Archives of neurology.

[17]  T. Iwatsubo,et al.  Aβ Immunotherapy: Intracerebral Sequestration of Aβ by an Anti-Aβ Monoclonal Antibody 266 with High Affinity to Soluble Aβ , 2009, The Journal of Neuroscience.

[18]  G. Bitan,et al.  Photo-induced cross-linking of unmodified proteins (PICUP) applied to amyloidogenic peptides. , 2009, Journal of visualized experiments : JoVE.

[19]  K. Blennow,et al.  Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment , 2009, Neurobiology of Aging.

[20]  J. Morris,et al.  The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals , 2008, Cerebral cortex.

[21]  Dong Jin Kim,et al.  Regulation of in vitro Aβ1-40 aggregation mediated by small molecules. , 2010, Journal of Alzheimer's disease : JAD.

[22]  David M. Rissin,et al.  Single-Molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations , 2010, Nature Biotechnology.

[23]  M. Vestling,et al.  Amyloid-β Oligomer Specificity Mediated by the IgM Isotype – Implications for a Specific Protective Mechanism Exerted by Endogenous Auto-Antibodies , 2010, PloS one.

[24]  Sang Won Seo,et al.  Seoul Neuropsychological Screening Battery-Dementia Version (SNSB-D): A Useful Tool for Assessing and Monitoring Cognitive Impairments in Dementia Patients , 2010, Journal of Korean medical science.

[25]  T. Tokuda,et al.  High-molecular weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients , 2010, Alzheimer's & Dementia.

[26]  T. Tokuda,et al.  High-molecular weight β-amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients , 2010, Alzheimer's & Dementia.

[27]  Sang Won Seo,et al.  Volume reduction in subcortical regions according to severity of Alzheimer’s disease , 2011, Journal of Neurology.

[28]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease , 2011, Neurology.

[29]  J. Kornak,et al.  Amyloid Vs Fdg-pet in the Differential Diagnosis of Ad And , 2022 .

[30]  R. Mayeux,et al.  Meta-analysis of plasma amyloid-β levels in Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[31]  John Seibyl,et al.  Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study , 2011, The Lancet Neurology.

[32]  Tamara B Harris,et al.  Association of plasma beta-amyloid level and cognitive reserve with subsequent cognitive decline. , 2011, JAMA.

[33]  N. Schupf,et al.  Nutrient intake and plasma β-amyloid , 2012, Neurology.

[34]  J. H. Viles,et al.  Human Serum Albumin Can Regulate Amyloid-β Peptide Fiber Growth in the Brain Interstitium , 2012, The Journal of Biological Chemistry.

[35]  M. Verbeek,et al.  Methods for analysis of amyloid-β aggregates. , 2012, Journal of Alzheimer's disease : JAD.

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

[37]  C. Rowe,et al.  Physical activity and amyloid-β plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing , 2013, Molecular Psychiatry.

[38]  A. Jeromin,et al.  CSF and Plasma Amyloid-β Temporal Profiles and Relationships with Neurological Status and Mortality after Severe Traumatic Brain Injury , 2014, Scientific Reports.

[39]  M. Peng,et al.  Plasma amyloid-β oligomers and soluble tumor necrosis factor receptors as potential biomarkers of AD. , 2014, Current Alzheimer research.

[40]  Dong Jin Kim,et al.  EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques , 2015, Nature Communications.

[41]  M. Sabbagh,et al.  Age dependence of brain β-amyloid deposition in Down syndrome , 2015, Neurology.

[42]  M. Sabbagh,et al.  Age dependence of brain β-amyloid deposition in Down syndrome , 2015, Neurology.

[43]  E. H. Jang,et al.  White Matter Changes May Precede Gray Matter Loss in Elderly with Subjective Memory Impairment , 2016, Dementia and Geriatric Cognitive Disorders.

[44]  E. H. Jang,et al.  White Matter Changes May Precede Gray Matter Loss in Elderly with Subjective Memory Impairment. , 2016, Dementia and geriatric cognitive disorders.

[45]  G. Taglialatela,et al.  Non-Demented Individuals with Alzheimer's Disease Neuropathology: Resistance to Cognitive Decline May Reveal New Treatment Strategies. , 2016, Current pharmaceutical design.

[46]  Jun-Young Lee,et al.  Head-to-head comparison of 11C-PiB and 18F-FC119S for Aβ imaging in healthy subjects, mild cognitive impairment patients, and Alzheimer's disease patients , 2017, Medicine.

[47]  Y. Yoo,et al.  A highly sensitive plasma-based amyloid-β detection system through medium-changing and noise cancellation system for early diagnosis of the Alzheimer’s disease , 2017, Scientific Reports.