Decoding senescent drivers in Alzheimer's disease: From bench to bedside.

Area of Science:

• Neuroscience
• Gerontology
• Cell Biology

Background:

• Alzheimer's disease (AD) is a leading cause of dementia, characterized by neurodegeneration.
• Cellular senescence, a hallmark of aging, is increasingly implicated in AD pathogenesis.
• Senescent cells in the AD brain release factors (SASP) that worsen neurotoxicity and neuroinflammation.

Purpose of the Study:

• To comprehensively review the molecular links between Alzheimer's disease and cellular senescence.
• To analyze the role of the senescent microenvironment in driving neurodegeneration.
• To evaluate senotherapeutics as potential novel treatments for AD.

Main Methods:

• Literature review and analysis of molecular mechanisms.
• Examination of the senescence-associated secretory phenotype (SASP) in AD.
• Evaluation of senolytic and senomorphic therapies.

Main Results:

• Senescent cells (neurons, glia, endothelial cells) are present in the AD brain.
• SASP exacerbates Aβ and tau pathology, promotes inflammation, and compromises the blood-brain barrier (BBB).
• A detrimental "senescence-neurodegeneration" cycle is established.

Conclusions:

• Cellular senescence is a key driver of neurodegeneration in Alzheimer's disease.
• Targeting senescent cells with senotherapeutics presents a promising therapeutic avenue for AD.
• Further research into senotherapeutics could lead to effective clinical management strategies for AD.