Skip to Content
Merck
CN
  • Pigment Epithelium-Derived Factor Plays a Role in Alzheimer's Disease by Negatively Regulating Aβ42.

Pigment Epithelium-Derived Factor Plays a Role in Alzheimer's Disease by Negatively Regulating Aβ42.

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics (2018-05-08)
Mao Huang, Weiwei Qi, Shuhuan Fang, Ping Jiang, Cong Yang, Yousheng Mo, Chang Dong, Yan Li, Jun Zhong, Weibin Cai, Zhonghan Yang, Ti Zhou, Qi Wang, Xia Yang, Guoquan Gao
ABSTRACT

Alzheimer's disease (AD) is the most common cause of dementia. Pigment epithelium-derived factor (PEDF), a unique neurotrophic protein, decreases with aging. Previous reports have conflicted regarding whether the PEDF concentration is altered in AD patients. In addition, the effect of PEDF on AD has not been documented. Here, we tested serum samples of 31 AD patients and 271 normal controls. We found that compared to PEDF levels in young and middle-aged control subjects, PEDF levels were reduced in old-aged controls and even more so in AD patients. Furthermore, we verified that PEDF expression was much lower and amyloid β-protein (Aβ)42 expression was much higher in senescence-accelerated mouse prone 8 (SAMP8) strain mice than in senescence-accelerated mouse resistant 1 (SAMR1) control strain mice. Accordingly, high levels of Aβ42 were also observed in PEDF knockout (KO) mice. PEDF notably reduced cognitive impairment in the Morris water maze (MWM) and significantly downregulated Aβ42 in SAMP8 mice. Mechanistically, PEDF downregulated presenilin-1 (PS1) expression by inhibiting the c-Jun N-terminal kinase (JNK) pathway. Taken together, our findings demonstrate for the first time that PEDF negatively regulates Aβ42 and that PEDF deficiency with aging might play a crucial role in the development of AD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Pigment Epithelium Derived Factor Antibody, clone 10F12.2, clone 10F12.2, Chemicon®, from mouse