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Open AccessArticle

Reduced Levels of Cerebrospinal Fluid/Plasma Aβ40 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats

1
George & Anne Ryan Institute for Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA
2
Enzo Life Sciences, 10 Executive Blvd, Farmingdale, NY 11735, USA
3
Department of Anesthesiology, Yale University, New Haven, CT 06520, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 303; https://doi.org/10.3390/ijms21010303
Received: 2 December 2019 / Revised: 28 December 2019 / Accepted: 30 December 2019 / Published: 1 January 2020
(This article belongs to the Special Issue Cerebral Amyloid Angiopathy: Causes, Diagnosis and Treatment)
The accumulation of fibrillar amyloid β-protein (Aβ) in blood vessels of the brain, the condition known as cerebral amyloid angiopathy (CAA), is a common small vessel disease that promotes cognitive impairment and is strongly associated with Alzheimer’s disease. Presently, the clinical diagnosis of this condition relies on neuroimaging markers largely associated with cerebral macro/microbleeds. However, these are markers of late-stage disease detected after extensive cerebral vascular amyloid accumulation has become chronic. Recently, we generated a novel transgenic rat model of CAA (rTg-DI) that recapitulates multiple aspects of human CAA disease with the progressive accumulation of cerebral vascular amyloid, largely composed of Aβ40, and the consistent emergence of subsequent microbleeds. Here, we investigated the levels of Aβ40 in the cerebrospinal fluid (CSF) and plasma of rTg-DI rats as CAA progressed from inception to late stage disease. The levels of Aβ40 in CSF and plasma precipitously dropped at the early onset of CAA accumulation at three months of age and continued to decrease with the progression of disease. Notably, the reduction in CSF/plasma Aβ40 levels preceded the emergence of cerebral microbleeds, which first occurred at about six months of age, as detected by in vivo magnetic resonance imaging and histological staining of brain tissue. These findings support the concept that reduced CSF/plasma levels of Aβ40 could serve as a biomarker for early stage CAA disease prior to the onset of cerebral microbleeds for future therapeutic intervention. View Full-Text
Keywords: cerebral amyloid angiopathy; amyloid β-protein; transgenic rat; cerebrospinal fluid; biomarker cerebral amyloid angiopathy; amyloid β-protein; transgenic rat; cerebrospinal fluid; biomarker
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MDPI and ACS Style

Zhu, X.; Xu, F.; Hoos, M.D.; Lee, H.; Benveniste, H.; Van Nostrand, W.E. Reduced Levels of Cerebrospinal Fluid/Plasma Aβ40 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats. Int. J. Mol. Sci. 2020, 21, 303. https://doi.org/10.3390/ijms21010303

AMA Style

Zhu X, Xu F, Hoos MD, Lee H, Benveniste H, Van Nostrand WE. Reduced Levels of Cerebrospinal Fluid/Plasma Aβ40 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats. International Journal of Molecular Sciences. 2020; 21(1):303. https://doi.org/10.3390/ijms21010303

Chicago/Turabian Style

Zhu, Xiaoyue; Xu, Feng; Hoos, Michael D.; Lee, Hedok; Benveniste, Helene; Van Nostrand, William E. 2020. "Reduced Levels of Cerebrospinal Fluid/Plasma Aβ40 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats" Int. J. Mol. Sci. 21, no. 1: 303. https://doi.org/10.3390/ijms21010303

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