Beyond CSF and Neuroimaging Assessment: Evaluating Plasma miR-145-5p as a Potential Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease

Alzheimer’s
disease (AD) is the most common cause
of dementia.
New strategies for the early detection of MCI and sporadic AD are
crucial for developing effective treatment options. Current techniques
used for diagnosis of AD are invasive and/or expensive, so they are
not suitable for population screening. Cerebrospinal fluid (CSF) biomarkers
such as amyloid β1–42 (Aβ1–42), total tau
(T-tau), and phosphorylated tau181 (P-tau181) levels are core biomarkers
for early diagnosis of AD. Several studies have proposed the use of
blood-circulating microRNAs (miRNAs) as potential novel early biomarkers
for AD. We therefore applied a novel approach to identify blood-circulating
miRNAs associated with CSF biomarkers and explored the potential of
these miRNAs as biomarkers of AD. In total, 112 subjects consisting
of 28 dementia due to AD cases, 63 MCI due to AD cases, and 21 cognitively
healthy controls were included. We identified seven Aβ1–42-associated
plasma miRNAs, six P-tau181-associated plasma miRNAs, and nine Aβ1–42-associated
serum miRNAs. These miRNAs were involved in AD-relevant biological
processes, such as PI3K/AKT signaling. Based on this signaling pathway,
we constructed an miRNA-gene target network, wherein miR-145-5p has
been identified as a hub. Furthermore, we showed that miR-145-5p performs
best in the prediction of both AD and MCI. Moreover, miR-145-5p also
improved the prediction performance of the mini-mental state examination
(MMSE) score. The performance of this miRNA was validated using different
datasets including an RT-qPCR dataset from plasma samples of 23 MCI
cases and 30 age-matched controls. These findings indicate that blood-circulating
miRNAs that are associated with CSF biomarkers levels and specifically
plasma miR-145-5p alone or combined with the MMSE score can potentially
be used as noninvasive biomarkers for AD or MCI screening in the general
population, although studies in other AD cohorts are necessary for
further validation.