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Diagnosing Alzheime...
Diagnosing Alzheimer's Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe.
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Black, Stefanie A G (author)
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Stepanchuk, Anastasiia A (author)
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Templeton, George W (author)
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Hernandez, Yda (author)
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Ota, Tomoko (author)
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Roychoudhury, Shyamosree (author)
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Smith, Eric E (author)
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Barber, Philip A (author)
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Ismail, Zahinoor (author)
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Fischer, Karyn (author)
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Zwiers, Angela (author)
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Poulin, Marc J (author)
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Zetterberg, Henrik, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Stys, Peter K (author)
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Tsutsui, Shigeki (author)
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(creator_code:org_t)
- 2022
- 2022
- English.
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In: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 85:4, s. 1721-1734
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Abstract
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- Toxic amyloid-β (Aβ) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials.To develop a novel method for early Alzheimer's disease (AD) detection, we used blood leukocytes, that could act as "sentinels" after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy.Formalin-fixed peripheral blood mononuclear cells (PBMCs) from cognitively healthy control (HC) subjects, mild cognitive impairment (MCI) and AD patients were stained with the fluorescent amyloid probe K114, and imaged. Results were validated against cerebrospinal fluid (CSF) biomarkers and clinical diagnosis.K114-labeled leukocytes exhibited distinctive fluorescent spectral signatures in MCI/AD subjects. Comparing subjects with single CSF biomarker-positive AD/MCI to negative controls, our technique yielded modest AUCs, which improved to the 0.90 range when only MCI subjects were included in order to measure performance in an early disease state. Combining CSF Aβ 42 and t-Tau metrics further improved the AUC to 0.93.Our method holds promise for sensitive detection of AD-related protein misfolding in circulating leukocytes, particularly in the early stages of disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Black, Stefanie ...
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Stepanchuk, Anas ...
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Templeton, Georg ...
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Hernandez, Yda
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Ota, Tomoko
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Roychoudhury, Sh ...
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show more...
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Smith, Eric E
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Barber, Philip A
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Ismail, Zahinoor
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Fischer, Karyn
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Zwiers, Angela
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Poulin, Marc J
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Blennow, Kaj, 19 ...
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Zetterberg, Henr ...
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Stys, Peter K
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Tsutsui, Shigeki
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Alzhe ...
- By the university
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University of Gothenburg