Expression of BC1 Impairs Spatial Learning and Memory in Alzheimer’s Disease Via APP Translation

• DOI: 10.1007/s12035-017-0820-z
• Publication Date: 2017-11-12T23:38:38Z
• Authors: Tongmei Zhang; Pei Pang; Zemin Fang; Yu Guo; Hao Li; Xinyan Li; Tian Tian; Xin Yang; Wenting Chen; Shu Shu; Na Tang; Jianhua Wu; Houze Zhu; Lei Pei; Dan Liu; Qing Tian; Jian Wang; Lin Wang; Ling-Qiang Zhu; Youming Lu
• Keywords: Memory Disorders; 0303 health sciences; Spatial Learning; Mice, Transgenic; 3. Good health; Mice, Inbred C57BL; Amyloid beta-Protein Precursor; Fragile X Mental Retardation Protein; 03 medical and health sciences; Alzheimer Disease; Memory; Protein Biosynthesis; Animals; RNA, Long Noncoding; RNA, Messenger

Aggregation of amyloid-β (Aβ) peptides, which are the cleavage products of amyloid precursor protein (APP), is a major pathological hallmark in the brain of Alzheimer's disease (AD). Now, we know little about the roles of APP translation in the disease progression of AD. Here, we show that BC1, a long noncoding RNA (lncRNA), is expressed in the brain of AD mice. BC1 induces APP mRNA translation via association with a fragile X syndrome protein (FMRP). Inhibition of BC1 or BC1-FMRP association in AD mice blocks aggregation of Aβ in the brain and protects against the spatial learning and memory deficits. Expression of exogenous BC1 in excitatory pyramidal neurons of mice induces Aβ peptides accumulation and the spatial learning and memory impairments. This study provides a novel mechanism underlying aggregation of Aβ peptides via BC1 induction of APP mRNA translation and hence warrants a promising target for AD therapy.