The blood-based diagnosis has a potential to provide an alternative approach for easy diagnosis of Alzheimer's disease (AD) with less invasiveness and low-cost. However, present blood-based AD diagnosis mainly focuses on measuring the plasma Aβ level because no other biomarkers are found to possess evident transport mechanisms to pass the blood-brain barrier. In order to avoid diagnosing non-demented individuals with Aβ abnormality, finding additional biomarkers to supplement plasma Aβ is essential. In this study, we introduce potential neurodegenerative biomarkers for blood-based diagnosis. We observed severe splenomegaly and structural destruction in the spleen with significantly decreased B lymphocytes in senile APPswe, PS1M146V and TauP301L transgenic mice. We also found that inflammatory cytokines associated with splenic dysfunction were altered in the plasma of these mice. These findings suggest potential involvement of the splenic dysfunction in AD and the importance of biomarker level alterations in the plasma as putative diagnostic targets for AD.
Bibliographical noteFunding Information:
This work was funded by Korea Health Industry Development Institute (KHIDI, HI14C3319) and KIST Institutional Programs (2E25732, 2E25240 and 2E25473). The authors thank Dr. Soo Min Cho (Korea Institute of Science and Technology) and Hyunjin Vincent Kim (Korea Institute of Science and Technology) for technical assistance of plasma and CSF preparation; Yakdol Cho (Korea Institute of Science and Technology) for animal maintenance and preparation; Prof. Joo-Won Park (Ewha Womans University), Prof. Woo-Jae Park (Gachon University) and So-Yeon Kim (Ewha Womans University) for technical assistance of FACS analysis and immunostaining. The authors appreciate Dr. Hye Yun Kim (Korea Institute of Science and Technology) for scientific advices.
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