Lead-induced hypertension and cognitive dysfunction: brain amyloid pathology

Area of Science:

• Neuroscience
• Toxicology
• Pharmacology

Background:

• Lead (Pb) exposure is linked to cognitive decline and Alzheimer's disease (AD) pathology, potentially via hypertension.
• The role of mineralocorticoid receptor (MR) signaling in Pb-induced AD exacerbation is not fully understood.

Purpose of the Study:

• To investigate if Pb-induced hypertension exacerbates amyloid pathology through MR activation.
• To evaluate amlodipine and spironolactone as potential therapeutics in an AD mouse model.

Main Methods:

• APPSwDI transgenic mice were exposed to lead acetate for 8 weeks.
• Mice received concurrent treatment with amlodipine or spironolactone.
• Cognitive function, blood pressure, neuroinflammation, oxidative stress, and brain amyloid deposition were assessed.

Main Results:

• Pb exposure increased blood pressure, impaired cognition, elevated inflammatory markers (IL-1β, IL-6), and enhanced brain amyloid burden.
• MR expression in brain tissue was upregulated post-Pb exposure.
• Both drugs improved cognition and reduced neuroinflammation; spironolactone was more effective in suppressing MR expression and amyloid deposition.

Conclusions:

• Lead exposure exacerbates AD-like pathology via MR-related hypertensive and inflammatory pathways.
• MR antagonism with spironolactone provides significant neuroprotection in this model.
• Targeting MR signaling presents a potential therapeutic strategy for environmentally induced AD risk.