GDF11 Rejuvenates Cerebrovascular Structure and Function in an Animal Model of Alzheimer’s Disease

Article type: Research Article

Authors: Zhang, Wei^{a; 1} | Guo, Yi^{b; 1} | Li, Bo^a | Zhang, Qi^c | Liu, Jian-hui^d | Gu, Guo-jun^b | Wang, Jin-hong^e | Bao, Rui-kang^f | Chen, Yu-jie^{g; *} | Xu, Jian-rong^{a; *}

Affiliations: [a] Department of Medical Imaging, Renji Hospital, Medical School of Jiaotong University, Shanghai, P.R. China | [b] Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai, P.R. China | [c] Department of Blood Transfusion, Huashan Hospital, Fudan University, Shanghai, P.R. China | [d] Department of Anesthesiology, Tongji Hospital, Medical School of Tongji University, Shanghai, P.R. China | [e] Shanghai Mental Health Center, Medical School of Jiaotong University, Shanghai, P.R. China | [f] Department of Radiotherapy, Suzhou municipal hospital, Nanjing Medical University, Jiangsu Province, P.R. China | [g] Uli Schwarz Public Central Lab, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai, P.R. China

Correspondence: [*] Correspondence to: Xu Jian-rong, Department of Medical Imaging, Renji Hospital, Medical School of Jiaotong University, No. 160, Pujian Road, Pudong District, Shanghai 200127, P. R. China. Tel.: +86 21 58752345; Fax: +86 21 58753259; E-mails: [email protected]; [email protected] and Chen Yu-jie, Uli Schwarz Public Central Lab, CAS-MPG Partner Institute for Computational Biology (PICB), Room 500, SIBS Building, 320, YueYang Rd. Shanghai 200031, China. Tel.: +86 021 54920415; Fax: +86 21 6838 3354; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Cerebral amyloid angiopathy (CAA) is present in up to 90% of patients with Alzheimer's disease (AD), and may interact with classical neuropathology to exacerbate cognitive decline. Since growth differentiation factor 11 (GDF11) can activate vascular remodeling, we tested its effects on cognitive function and neuroinflammatory changes of AD model mice. We intravenously administered GDF11 or vehicle daily to 12-month-old transgenic mice overexpressing the amyloid-β protein precursor (AβPP)/PS1). Cognitive function was monitored using the Morris water maze, and after conclusion of the treatment, we assessed the morphology and presence of inflammatory markers in the cerebral vasculature. Subchronic treatment of adult AβPP/PS1 mice with GDF11 rescued cognitive function and ameliorated cerebrovascular function. In particular, the de novo genesis of small blood vessels and the expression of vascular-related proteins were significantly higher than in the vehicle-treated AβPP/PS1 mice, whereas the expressions of the inflammatory markers Iba-1 and GFAP significantly decreased in proportion to the lower ratio of two forms of amyloid-β (Aβ40/42). Daily intravenous treatment with GDF11-injection can rejuvenate respects of cognition and cerebrovascular changes in AD mice.

Keywords: Alzheimer’s disease, cerebral amyloid angiopathy, cerebral blood flow, growth differentiation factor 11, neuroinflammation

DOI: 10.3233/JAD-170474

Journal: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 807-819, 2018