Functional Pathological Features and Molecular Markers in Alzheimer's Disease

Area of Science:

• Neuroscience
• Pathology
• Biomarkers

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-β plaques and tau pathology.
• AD progression involves interconnected processes: neuroinflammation, neuronal cell death, synaptic dysfunction, blood-brain barrier (BBB) breakdown, and myelin/axonal damage, leading to cognitive decline.

Purpose of the Study:

• To present a cell-centered framework linking key molecular markers to AD progression processes.
• To provide insights into AD pathogenesis and identify potential diagnostic and therapeutic targets.

Main Methods:

• Review of literature on Alzheimer's disease pathogenesis.
• Integration of data on molecular markers associated with neuroinflammation (e.g., Iba1, GFAP, IL-1β), neuronal cell death (e.g., caspase-3, GPX4), synaptic dysfunction (e.g., synaptophysin), BBB integrity, and myelin/axonal damage (e.g., NfL).

Main Results:

• Neuroinflammation involves activated microglia/astrocytes and markers like Iba1, GFAP, IL-1β.
• Neuronal death pathways include apoptosis, ferroptosis, pyroptosis, necroptosis with markers like caspase-3, GPX4.
• Synaptic dysfunction, BBB breakdown, and myelin/axonal damage are linked to markers such as synaptophysin, NfL, disrupting neural connectivity.

Conclusions:

• An integrated cell-centered framework highlights the dynamic interplay of AD pathologies.
• Key molecular markers associated with these processes offer potential for AD diagnosis, monitoring, and therapeutic intervention.