Recent studies indicated that sortilin-related receptor 1 (SORL1) is a risk gene 
for late-onset Alzheimer's disease (AD), although its role in the aetiology 
and/or progression of this disorder is not fully understood. Here, we report the 
finding of a non-coding (nc) RNA (hereafter referred to as 51A) that maps in 
antisense configuration to intron 1 of the SORL1 gene. 51A expression drives a 
splicing shift of SORL1 from the synthesis of the canonical long protein variant 
A to an alternatively spliced protein form. This process, resulting in a 
decreased synthesis of SORL1 variant A, is associated with impaired processing 
of amyloid precursor protein (APP), leading to increased Aβ formation. 
Interestingly, we found that 51A is expressed in human brains, being frequently 
upregulated in cerebral cortices from individuals with Alzheimer's disease. 
Altogether, these findings document a novel ncRNA-dependent regulatory pathway 
that might have relevant implications in neurodegeneration.