*Article* **Liver Growth Factor "LGF" as a Therapeutic Agent for Alzheimer's Disease**

**Rafael Gonzalo-Gobernado 1,2,**†**, Juan Perucho 1,**†**, Manuela Vallejo-Muñoz 1,**†**, Maria José Casarejos 1, Diana Reimers 1, Adriano Jiménez-Escrig 1,3, Ana Gómez 1, Gonzalo M. Ulzurrun de Asanza <sup>1</sup> and Eulalia Bazán 1,\***


Received: 23 October 2020; Accepted: 29 November 2020; Published: 2 December 2020

**Abstract:** Alzheimer's disease (AD) is a progressive degenerative disorder and the most common cause of dementia in aging populations. Although the pathological hallmarks of AD are well defined, currently no effective therapy exists. Liver growth factor (LGF) is a hepatic albumin–bilirubin complex with activity as a tissue regenerating factor in several neurodegenerative disorders such as Parkinson's disease and Friedreich's ataxia. Our aim here was to analyze the potential therapeutic effect of LGF on the APPswe mouse model of AD. Twenty-month-old mice received intraperitoneal (i.p.) injections of 1.6 μg LGF or saline, twice a week during three weeks. Mice were sacrificed one week later, and the hippocampus and dorsal cortex were prepared for immunohistochemical and biochemical studies. LGF treatment reduced amyloid-β (Aβ) content, phospho-Tau/Tau ratio and the number of Aβ plaques with diameter larger than 25 μm. LGF administration also modulated protein ubiquitination and HSP70 protein levels, reduced glial reactivity and inflammation, and the expression of the pro-apoptotic protein Bax. Because the administration of this factor also restored cognitive damage in APPswe mice, we propose LGF as a novel therapeutic tool that may be useful for the treatment of AD.

**Keywords:** liver growth factor; Alzheimer's disease; inflammation; neuroprotection; microglia; Tg2576 transgenic mice; amyloid-beta
