Company: APM
Filing Date: 2025-07-15
Form Type: DRS
Source: 0001213900-25-063899
Chunk: 276

Company: Aptorum Group Ltd
Filing Date: 2025-07-15
Form: DRS
Chunk 276
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 of biomarkers to enable detection and diagnosis even earlier than is now possible and to distinguish different
forms of dementia from one another, as well as to leverage technologies that enable characterization of individual cells to advance dementia
research.

Since cognitive testing cannot reliably identify
patients in pre-symptomatic stages of AD, effective biomarkers are necessary for successful patient enrollment and treatment monitoring.

The pathology of AD is characterized by neuronal
death in several specific regions of the brain, including the hippocampus and cortex. However, the neuronal loss is a relatively late
event in the disease progression and is typically preceded by metabolic changes, including formation of beta-amyloid plaques and tau protein
tangles, synaptic dysfunction, synaptic loss, neurite retraction, and the appearance of other abnormalities, such as axonal transport
defects. Figure below (adapted from Jack et al. (2010) Lancet Neurol 9:119; Sperling et al. (2011) Alzheimers Dement., 7:280)
depicts stages of AD progression from preclinical stage to dementia. To identify early stages of neurodegeneration, those preceding clinical
manifestation, DiamiR focuses on detecting synaptic dysfunction / loss in hippocampus, a brain region affected early on during AD development.

<div align='center'>Stages of Neurodegeneration

143</div>

MCI, the first stage of symptomatic
AD that can be diagnosed by the cognitive function analysis, is a condition that can also be indicative of other NDs. Not all MCI patients
develop AD: (1) it is estimated that MCI patients convert to dementia at a rate of 10-15% annually; at the same time (2) some MCI patients
stabilize (do not develop AD) or revert to normal status; (3) approximately 20% of those MCI patients who do convert to dementia, are
diagnosed with vascular, Lewy body, Huntington, Parkinson, and other non-AD dementias; and finally (4) disease progression varies for
AD patients from slow to intermediate to rapid.

New research consortiums such as the Alzheimer’s Disease Neuro-imaging
Initiative (ADNI) in the US (http://www.adni-info.org/) and similar projects in other countries have contributed to significant progress
in early detection of AD with high sensitivity and specificity by imaging techniques and analysis of protein biomarkers in cerebrospinal
fluid. However, the high