Vacuolar Protein-Sorting Proteins Are Reduced Even Before Cognitive Decline in a Mouse Model of Alzheimer’s Disease

Article type: Short Communication

Authors: Shinagawa, Hijiri | Ohuchi, Kazuki | Goto, Yuya | Hashimoto, Kohei | Kijima, Hideki | Maekawa, Shogo | Kurita, Hisaka | Inden, Masatoshi^{; *}

Affiliations: Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan

Correspondence: [*] Correspondence to: Masatoshi Inden, PhD, Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, 1-1-1 Gifu 501-1196, Japan. Tel./Fax.: +81 58 230 8100; E-mail: inden@gifu-pu.ac.jp.

Abstract: Currently, interventions from the preclinical stage are considered necessary for the treatment of Alzheimer’s disease (AD). Previous studies have reported that vacuolar protein-sorting protein (VPS), a retromer construct, is involved in the pathogenic mechanisms of AD and Parkinson’s disease. This study evaluated VPS26, VPS29, and VPS35 before and after the onset of cognitive decline in an App knock-in mouse model of AD that more closely resembles the human pathology than previous AD models. The results showed that the expression of VPS26 and VPS35 decreased before the onset of cognitive decline, suggesting the possibility of anti-amyloid-β disease-modifying treatment targeting these proteins.

Keywords: Alzheimer’s disease, amyloid-β, retromer, vacuolar protein-sorting protein

DOI: 10.3233/JAD-230686

Journal: Journal of Alzheimer's Disease, vol. 96, no. 3, pp. 1011-1017, 2023