Company: APM
Filing Date: 2025-12-05
Form Type: 424B5
Source: 0001213900-25-118752
Chunk: 299

Company: Aptorum Group Ltd
Filing Date: 2025-12-05
Form: 424B5
Chunk 299
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 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</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 cost, around $3,000, and invasiveness of these methods make
their application to primary screening of large populations impractical. Thus, there is a great need for an accurate and cost-effective
blood-based test for early detection of AD. (Cost-effectiveness of using amyloid positron emission tomography in individuals with mild
cognitive impairment. Lee et. al., Cost Effectiveness and Resource Allocation volume 19, Article number: 50 (2021)).

A recent article “The
Financial Consequences of Undiagnosed Memory Disorders” published in May 2024 (Gresenz, et al., Federal Reserve Bank of New York
Staff Reports, no. 1106; 2024)) examined the effects of pre-symptomatic and early symptomatic brain health conditions, such as neurodegenerative
diseases