Peripheral Inflammation Is Associated With Greater Neuronal Injury and Lower Episodic Memory Among Late Middle-Aged...

Area of Science:

• Neuroscience
• Immunology
• Gerontology

Background:

• Alzheimer's disease (AD) early detection relies on understanding preclinical mechanisms.
• Amyloid-beta (Aβ) and tau pathologies are key, but peripheral factors are underexplored.
• Investigating peripheral inflammation's role in early AD pathogenesis is crucial.

Purpose of the Study:

• To examine tau positron emission tomography (PET) and peripheral inflammation in relation to Aβ burden and neurodegeneration.
• To assess the association of these markers with cognitive function and comorbidities in cognitively unimpaired adults.
• To explore the interplay between central and peripheral mechanisms in early AD.

Main Methods:

• Utilized 18F-MK6240 tau PET imaging in 132 cognitively unimpaired Hispanic adults.
• Measured plasma neurofilament light (NfL) for neuronal injury and peripheral inflammatory markers.
• Analyzed associations between Aβ, tau, inflammation, NfL, cognitive performance, and comorbidities (BMI, DM).

Main Results:

• Early tau deposition was observed even without significant NfL elevation.
• Peripheral inflammation correlated with NfL but not directly with Aβ or tau.
• Episodic memory impairment was linked to inflammation and NfL, not Aβ or tau.
• Aβ and tau were influenced by genetics and sex; inflammation by NfL, BMI, and DM.

Conclusions:

• Peripheral inflammation and neurodegeneration markers are associated with early cognitive changes in preclinical AD.
• Findings suggest integrating peripheral markers into AD progression models for better risk stratification.
• Targeting inflammation and vascular health may offer novel strategies for AD prevention.