Company: APM
Filing Date: 2025-12-05
Form Type: 424B5
Source: 0001213900-25-118752
Chunk: 294

Company: Aptorum Group Ltd
Filing Date: 2025-12-05
Form: 424B5
Chunk 294
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 DiamiR hypothesizes that changes in plasma levels of circulating miRNAs
known to be enriched in specific regions of the brain involved in a disease pathology are more likely to reflect associated pathologic
processes than changes in levels of ubiquitous miRNAs or other brain-enriched miRNAs. DiamiR analyzed expression and secretion of neurite/synapse
specific miRNAs, which could be affected by neurite/synapse dysfunction and destruction characteristic of early stages of neurodegeneration.
Since these cellular neurodegenerative processes occur 10+ years prior to any manifestation of dementia and Alzheimer’s symptoms,
a miRNA testing platform has the potential to identify at-risk subject years before symptoms arise.

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To compensate for processes
unrelated directly to a disease pathology, e.g. changes in blood-brain barrier permeability, DiamiR employed the “biomarker pair”
approach normalizing levels of miRNAs enriched in neurons of affected brain areas by levels of other brain-enriched miRNAs expressed in
brain areas or cell types not involved in early stages of disease pathology. DiamiR has also found that high correlation of plasma concentrations
of miRNAs in a candidate biomarker miRNA pair is critical for achieving high sensitivity and specificity of the pair as a biomarker. This
finding significantly improves the selection of optimal miRNA pairs. Advantages and disadvantages of “Organ/Cell Specific Analysis”
developed by DiamiR vs. other approaches to identifying miRNA biomarkers are summarized in the table above.

In summary, miRNAs are powerful biomarkers, because:

| ● | certain miRNAs are enriched in |

| ● | specific organs in the body (e.g. brain) |

| ● | organ regions or tissues in an organ (e.g. hippocampus) |

| ● | cell types (e.g. neurons) |

| ● | cellular compartments within a cell (e.g. neurites, synapses) |

| ● | miRNAs appear in blood because they |

| ● | are secreted/excreted into extracellular space in normal cellular 
 processes                                                         |

| ● | can cross the blood-brain barrier |

| ● | are stable in circulation |

| ● | Mature technologies are available for miRNA detection |

| ● | miRNAs are reflective of the biology of the disease at the 
 time of biological samples are collected                   |

| ● | miRNAs are stable analytes and can be