The contribution of the autosomal dominant mutations to the etiology of familial 
Alzheimer's disease (AD) is well characterized. However, the molecular 
mechanisms contributing to sporadic AD are less well understood. Increased 
ceramide levels have been evident in AD patients. We previously reported that 
increased ceramide levels, regulated by increased serine palmitoyltransferase 
(SPT), directly mediate amyloid β (Aβ) levels. Therefore, we inhibited SPT in an 
AD mouse model (TgCRND8) through subcutaneous administration of L-cylcoserine. 
The cortical Aβ₄₂ and hyperphosphorylated tau levels were down-regulated with 
the inhibition of SPT/ceramide. Positive correlations were observed among 
cortical SPT, ceramide, and Aβ₄₂ levels. With no evident toxic effects observed, 
inhibition of SPT could be a safe therapeutic strategy to ameliorate the AD 
pathology. We previously observed that miR-137, -181c, -9, and 29a/b 
post-transcriptionally regulate SPT levels, and the corresponding miRNA levels 
in the blood sera are potential diagnostic biomarkers for AD. Here, we observe a 
negative correlation between cortical Aβ₄₂ and sera Aβ₄₂, and a positive 
correlation between cortical miRNA levels and sera miRNA levels suggesting their 
potential as noninvasive diagnostic biomarkers.