Alzheimer's Imaging Consortium

Area of Science:

• Neuroscience
• Neuropathology
• Radiology

Background:

• The locus coeruleus (LC) is an early site of tau pathology in Alzheimer's disease (AD), preceding clinical symptoms.
• Investigating LC integrity in relation to amyloid and tau deposition is crucial for understanding early AD.
• Asymptomatic, at-risk older adults provide a unique window into preclinical AD changes.

Purpose of the Study:

• To determine the association between locus coeruleus (LC) integrity and in vivo cortical amyloid and tau deposition.
• To explore these relationships in asymptomatic individuals with a familial risk for AD.
• To assess potential longitudinal changes and modulatory effects of amyloid on tau-LC associations.

Main Methods:

• Utilized MRI (T1w, neuromelanin-sensitive) and PET imaging (18F-NAV4694, 18F-flortaucipir) in 208 healthy older adults (PREVENT-AD cohort).
• Quantified cortical amyloid and tau using SUVR and LC integrity via LC_CNR.
• Employed robust linear mixed-effects models and linear regression, with FDR correction for multiple comparisons.

Main Results:

• Negative associations were found between LC integrity and cortical amyloid across most regions.
• Cortical tau associations with LC integrity were localized to temporal and inferior parietal regions.
• These associations were primarily observed at baseline, with no significant longitudinal effects. Global amyloid modulated the tau-LC relationship.

Conclusions:

• Locus coeruleus degeneration correlates with increased amyloid and tau pathology in asymptomatic individuals at risk for AD.
• These findings support the model of the LC as a central component in the earliest pathophysiological stages of AD.
• The LC's integrity is a potential biomarker for early AD-related changes.