Bridging systemic metabolic dysfunction and Alzheimer's disease: the liver interface.

Area of Science:

• Neuroscience
• Metabolic Disorders
• Hepatology

Background:

• Alzheimer's disease (AD) is increasingly understood as a systemic disorder linked to metabolic dysfunction.
• The liver plays a critical role in brain health via the liver-brain axis, influencing AD pathogenesis.
• Key liver functions impacting AD include beta-amyloid (Aβ) clearance and metabolic regulation.

Purpose of the Study:

• To review the current understanding of liver-brain crosstalk in Alzheimer's disease.
• To elucidate the mechanistic role of hepatokines in linking metabolic dysfunction to neurodegeneration.
• To highlight the diagnostic and therapeutic potential of hepatokines in AD.

Main Methods:

• Literature review synthesizing current knowledge on the liver-brain axis in AD.
• Analysis of the role of hepatokines in regulating key AD pathological pathways.
• Examination of lifestyle interventions affecting hepatokine expression.

Main Results:

• Hepatokines, such as FGF21 and SELENOP, regulate crucial pathways including insulin sensitivity, lipid metabolism, oxidative stress, and neurotrophic support.
• These hepatokine-mediated pathways are closely associated with core AD pathologies like Aβ aggregation, tau hyperphosphorylation, and neuroinflammation.
• Metabolic disorders significantly influence AD progression through liver-brain communication.

Conclusions:

• The liver is a key mediator bridging metabolic dysfunction and neurodegeneration in Alzheimer's disease.
• Hepatokines represent promising biomarkers and therapeutic targets for AD.
• Lifestyle interventions modulating hepatokines may offer novel strategies for AD prevention and treatment.