Background: Alzheimer’s disease (AD) is a type of disease frequently
occurs in the elderly population. Diagnosis and treatment methods for this
disease are still lacking, and more research is required. In addition, little is
known about the function of the circular RNAs (circRNAs) in AD. Methods:
In this research, RNA expression data of AD from the Gene Expression Omnibus
(GEO) database were downloaded. The expression levels of circRNAs in
cerebrospinal fluid samples of healthy participants and AD patients were measured
by reverse transcription‑quantitative PCR (RT-qPCR). The diagnosed value of
differential expressed circRNAs was analyzed with the Receiver operating
characteristic curve (ROC). Pathways related to circ_0001535 were found
using gene set enrichment analysis (GSEA) and Metascape. The direct interactions
between circ_0001535 and E2F transcription factor 1
(E2F1) or E2F1 and dihydrofolate reductase (DHFR) were verified using Chromatin
immunoprecipitation (ChIP) and RNA Binding Protein Immunoprecipitation (RIP)
assays. Cell Counting Kit-8 (CCK8) and flow cytometry were used to identify the
function of circ_0001535/E2F1/DHFR axis on the proliferation and
apoptosis of AD cells. Results: In total, 12 circRNAs have been linked
to AD diagnosis. The expression levels of 7 circRNAs differed between AD patients
and control groups. Circ_0001535 had the most diagnose value among
these circRNAs. Hence, circ_0001535 was regarded as a key circRNA in
the present study. E2F1/DHFR axis was predicted to be regulated by
circ_0001535. In addition, IP assays experiment results showed that
E2F1 could bind to the promoter region of DHFR and be regulated by
circ_0001535. In vitro results showed that
circ_0001535 overexpression could promote DHFR expression,
while E2F1 knock down could inhibit DHFR expression in SH-SY5Y
cells. Finally, rescue experiments suggested that circ_0001535 could
reduce A
