Systemic Inflammation Predicts Alzheimer Pathology in Community Samples without Dementia

Area of Science:

• Neuroscience
• Biochemistry
• Gerontology

Background:

• Neuroinflammation and oxidative stress (OS) are key factors in Alzheimer's disease (AD) development.
• The precise stage at which these pathological processes manifest in relation to AD biomarkers remains unclear.

Purpose of the Study:

• To investigate the associations between plasma markers of inflammation and OS with tau and amyloid-beta (Aβ) levels.
• To examine these associations in cognitively unimpaired middle-aged and older individuals.

Main Methods:

• Principal component analysis (PCA) was used to identify inflammatory and OS states from plasma markers.
• Associations between these identified states and AD biomarkers (tau, Aβ38, Aβ40, Aβ42) were analyzed.
• The study included middle-aged (52-56 years) and older-aged (72-76 years) participants without dementia.

Main Results:

• In middle-aged individuals, OS markers were most associated with tau and, to a lesser extent, Aβ levels.
• In older individuals, OS markers were associated with tau, while a separate inflammation component correlated with all AD biomarkers.
• Both inflammation and OS states showed associations with plasma AD biomarkers across age groups.

Conclusions:

• Inflammation and OS are associated with AD biomarkers in cognitively unimpaired individuals, suggesting early pathological changes.
• These findings highlight the potential role of early inflammation and OS in AD pathogenesis.
• Understanding these early associations may inform future preventative strategies for Alzheimer's disease.