GSE46579
What We Learned
  • Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. This study presents a novel miRNA-based signature for detecting AD from blood samples.
  • 12-miRNA signature can differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%.
  • The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies. 
  • Upregulated:
    1. brain-miR-112
    2. brain-miR-161
    3. hsa-let-7d-3p
    4. hsa-miR-5010-3p
    5. hsa-miR-26a-5p
    6. hsamiR-1285-5p
    7. hsa-miR-151a-3p
  • Downregulated:
    1. hsa-miR-103a-3p
    2. hsa-miR-107
    3. hsa-miR-532-5p
    4. hsa-miR-26b-5p
    5. hsa-let-7f-5p
  • As of today, final diagnosis of AD can only be achieved by autopsy making the identification of reliable, early, and non-invasive biomarkers a major challenge.
  • Finding such non-invasive, reliable diagnostic tools is of paramount importance as it appears that early intervention in the prodromal stage of AD or the identification and therapy of those patients with mild cognitive impairment who will transform to AD rapidly might be a possibility to delay the onset of AD substantially.
  • According to the S3 guidelines, an increased level of tau protein together with a decreased level of beta amyloid-1-42 provides strong evidence for the presence of AD.
  • Furthermore, combinatorial analysis of Aß levels and tau levels can discriminate between patients with stable mild cognitive impairment (MCI) and patients with progressive MCI into AD or other types of dementia with a sufficient diagnostic accuracy.
  • Molecular genetics analyses of common single nucleotide polymorphisms (SNPs) in genes such as presenilin or ApoE4 did not significantly improve risk estimation for the susceptibility of AD. 
  • Likewise, there is no consistent evidence for an association between AD and genetic variation of mitochondrial DNA (mtDNA).
  • There is increasing effort to develop molecular diagnostic markers that meet requirements like easy accessibility, for example, from blood, sufficiently high specificity and sensitivity, low costs and applicability by laboratories with standard equipment.
  • Moreover, Tan et al. provided evidence that the proteins p53 and p21 can be used to detect AD using blood samples. 
  • A receiver operating characteristic curve analysis revealed a specificity of 76% and a sensitivity of 84% for p53, 88% and 82% for p53(ser15), 80% and 75% for p21, and 84% and 68% for p21(thr145).
What We Did
  • A classification model has been built using Trainset. The selected probes were:
    1. hsa-mir-148b>hsa-mir-148b-5p
    2. hsa-mir-144>hsa-mir-144-5p
  • The model has been tested using Testset.