Amyloid-beta uptake by blood monocytes is reduced with ageing and Alzheimer's disease

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Deficits in amyloid-beta protein (Aβ) clearance are central to Alzheimer's disease (AD) pathogenesis.
• The specific role of peripheral blood monocytes in AD development and aging is not fully understood.

Purpose of the Study:

• To investigate changes in the Aβ phagocytosis function of peripheral monocytes during aging and in AD patients.
• To explore the relationship between monocyte Aβ uptake, blood Aβ levels, and receptor expression in AD.

Main Methods:

• Recruited 104 cognitively normal participants (aged 22-89), 24 AD patients, 25 age/sex-matched controls, 15 Parkinson's disease (PD) patients, and 15 age/sex-matched controls.
• Quantified Aβ₁₋₄₂ uptake by peripheral blood monocytes.
• Assessed the expression of Aβ uptake-related receptors, including Toll-like receptor 2 (TLR2).

Main Results:

• Monocyte Aβ₁₋₄₂ uptake decreased with age and was further reduced in AD patients, but not in PD patients.
• Reduced monocyte Aβ uptake correlated with increased blood Aβ₁₋₄₂ levels.
• Toll-like receptor 2 (TLR2) expression was significantly lower in monocytes from AD patients.

Conclusions:

• Peripheral blood monocytes play a role in regulating blood Aβ levels and may be implicated in AD pathogenesis.
• Impaired monocyte Aβ phagocytosis is a feature of aging and AD.
• Restoring monocyte Aβ uptake function presents a potential therapeutic avenue for Alzheimer's disease.