Haes, A. J., Chang, L., Klein, W. L. & Van Duyne, R. P. Detection of a biomarker for Alzheimer's Disease from synthetic and clinical samples using a nanoscale optical biosensor. J. Am. Chem. Soc. 127, 2264-2271

Department of Chemistry, Northwestern University, Evanston, Illinois, United States
Journal of the American Chemical Society (Impact Factor: 12.11). 03/2005; 127(7):2264-71. DOI: 10.1021/ja044087q
Source: PubMed


A nanoscale optical biosensor based on localized surface plasmon resonance (LSPR) spectroscopy has been developed to monitor the interaction between the antigen, amyloid-beta derived diffusible ligands (ADDLs), and specific anti-ADDL antibodies. Using the sandwich assay format, this nanosensor provides quantitative binding information for both antigen and second antibody detection that permits the determination of ADDL concentration and offers the unique analysis of the aggregation mechanisms of this putative Alzheimer's disease pathogen at physiologically relevant monomer concentrations. Monitoring the LSPR-induced shifts from both ADDLs and a second polyclonal anti-ADDL antibody as a function of ADDL concentration reveals two ADDL epitopes that have binding constants to the specific anti-ADDL antibodies of 7.3 x 10(12) M(-1) and 9.5 x 10(8) M(-1). The analysis of human brain extract and cerebrospinal fluid samples from control and Alzheimer's disease patients reveals that the LSPR nanosensor provides new information relevant to the understanding and possible diagnosis of Alzheimer's disease.

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    ABSTRACT: Amyloid formation is the pathological hallmark of type 2 diabetes (T2D) and Alzheimer's disease (AD). These diseases are marked by extracellular amyloid deposits of islet amyloid polypeptide (IAPP) in the pancreas and amyloid β (Aβ) in the brain. Since IAPP may enter the brain and disparate amyloids can cross-seed each other to augment amyloid formation, we hypothesized that pancreatic derived IAPP may enter the brain to augment misfolding of Aβ in AD. The corollaries for validity of this hypothesis are that IAPP enters the brain, augments Aβ misfolding, [3] associates with Aβ plaques, and most importantly plasma levels correlate with AD diagnosis. We demonstrate the first 3 corollaries that: (1) IAPP is present in the brain in human cerebrospinal fluid (CSF), (2) synthetic IAPP promoted oligomerization of Aβ in vitro, and (3) endogenous IAPP localized to Aβ oligomers and plaques. For the 4th corollary, we did not observe correlation of peripheral IAPP levels with AD pathology in either an African American cohort or AD transgenic mice. In the African American cohort, with increased risk for both T2D and AD, peripheral IAPP levels were not significantly different in samples with no disease, T2D, AD, or both T2D and AD. In the Tg2576 AD mouse model, IAPP plasma levels were not significantly elevated at an age where the mice exhibit the glucose intolerance of pre-diabetes. Based on this negative data, it appears unlikely that peripheral IAPP cross-seeds or "infects" Aβ pathology in AD brain. However, we provide novel and additional data which demonstrate that IAPP protein is present in astrocytes in murine brain and secreted from primary cultured astrocytes. This preliminary report suggests a potential and novel association between brain derived IAPP and AD, however whether astrocytic derived IAPP cross-seeds Aβ in the brain requires further research.
    Current Alzheimer Research 11/2014; 11(10). DOI:10.2174/1567205011666141107124538 · 3.89 Impact Factor
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    • "Recently gold, silver, cadmium, silicon and titanium nanoparticles have been synthesized using a number of bio-organisms [12–16]. By using their discrete physical, chemical and biological properties, the nanoparticles have been applied in various fields that include drug delivery [17], biosensors [18], bio imaging [19], anti-microbial activity [20], food preservation [21], etc. Ag-NPs are special materials with good biocompatibility, high surface volume ratio and fast electron communication features [22]. In this study, Ag-NPs have been synthesized using inexpensively and plentifully obtainable Acacia 0925-4005/© 2014 Elsevier B.V. All rights reserved. "
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    Sensors and Actuators B Chemical 10/2014; 202:177–184. DOI:10.1016/j.snb.2014.05.069 · 4.10 Impact Factor
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    • "Exploiting this characteristic, many studies in literature use AuNp for the development of sensitive sensors to specific molecules, such as casein [3], bovine serum albumin (BSA) [4], and human immunoglobulin (IgG) [5]. In addition, this result can be found in studies on the detection of antigens of cancer such as of the prostate [6] [7] and diseases such as Alzheimer's [8] [9]. In most of the cases, a monolayer of AuNp is attached to a substrate, usually glass [10]. "
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