FAM19A5 Deficiency Mitigates the Aß Plaque Burden and Improves Cognition in Mouse Models of Alzheimer's Disease.

Park, Sumi; Shahapal, Anu; Yoo, Sangjin; Kwak, Hoyun; Lee, Minhyeok; Lee, Sang-Myeong; Hwang, Jong-Ik; Seong, Jae Young

Park, Sumi; Shahapal, Anu; Yoo, Sangjin; Kwak, Hoyun; Lee, Minhyeok; Lee, Sang-Myeong; Hwang, Jong-Ik; Seong, Jae Young.

Afiliación

Park S; Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul 02841, Korea.
Shahapal A; Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul 02841, Korea.
Yoo S; Neuracle Science Co., Ltd., Seoul 02841, Korea.
Kwak H; Neuracle Science Co., Ltd., Seoul 02841, Korea.
Lee M; Neuracle Science Co., Ltd., Seoul 02841, Korea.
Lee SM; Neuracle Science Co., Ltd., Seoul 02841, Korea.
Hwang JI; Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul 02841, Korea.
Seong JY; Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul 02841, Korea.

Exp Neurobiol ; 33(4): 193-201, 2024 Aug 31.

Article en En | MEDLINE | ID: mdl-39266475

ABSTRACT

ABSTRACT

FAM19A5, a novel secretory protein highly expressed in the brain, is potentially associated with the progression of Alzheimer's disease (AD). However, its role in the AD pathogenesis remains unclear. Here, we investigated the potential function of FAM19A5 in the context of AD. We generated APP/PS1 mice with partial FAM19A5 deficiency, termed APP/PS1/FAM19A5+/LacZ mice. Compared with control APP/PS1 mice, APP/PS1/FAM19A5+/LacZ mice exhibited significantly lower Aß plaque density and prolonged the lifespan of the APP/PS1 mice. To further explore the therapeutic potential of targeting FAM19A5, we developed a FAM19A5 antibody. Administration of this antibody to APP/PS1 mice significantly improved their performance in the Y-maze and passive avoidance tests, indicating enhanced cognitive function. This effect was replicated in 5XFAD mice, a model of early-onset AD characterized by rapid Aß accumulation. Additionally, FAM19A5 antibody treatment in 5XFAD mice led to enhanced exploration of novel objects and increased spontaneous alternation behavior in the novel object recognition and Y-maze tests, respectively, indicating improved cognitive function. These findings suggest that FAM19A5 plays a significant role in AD pathology and that targeting with FAM19A5 antibodies may be a promising therapeutic strategy for AD.

Palabras clave

Alzheimer disease; Aß plaque; Cognitive function; FAM19A5

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Exp Neurobiol Año: 2024 Tipo del documento: Article Pais de publicación: