Patterns of amyloid accumulation in amyloid-negative cases

Area of Science:

• Neurodegenerative diseases
• Neuroimaging
• Biomarkers

Background:

• Amyloid staging models suggest regional amyloid-β (Aβ) abnormalities precede global positivity.
• Previous assumptions of homogeneous Aβ spread contrast with observed clinical heterogeneity.
• Understanding early Aβ deposition patterns is crucial for tracking disease progression.

Purpose of the Study:

• To investigate the existence of distinct Aβ deposition patterns in early amyloid accumulation.
• To analyze the demographic, clinical, cognitive, and biomarker correlates of identified Aβ patterns.
• To examine the association between Aβ patterns and longitudinal cognitive trajectories.

Main Methods:

• K-means clustering was applied to baseline amyloid positron emission tomography (PET) data from 151 individuals with negative Aβ PET scans (centiloid < 12).
• Clustering utilized 33 regional Aβ Standardized Uptake Value Ratios (SUVRs).
• Demographic, clinical, cognitive, biomarker data, and longitudinal neuropsychological assessments were analyzed in relation to identified clusters.

Main Results:

• Two distinct Aβ deposition patterns were identified: temporal predominant (TP) and cingulate predominant (CP).
• The temporal predominant (TP) cluster showed significantly higher tau deposition compared to the cingulate predominant (CP) cluster.
• A trend towards a higher rate of cognitive decline was observed in the TP group compared to the CP group.

Conclusions:

• This study suggests two distinct patterns of early amyloid-β accumulation exist.
• These patterns are differentially associated with tau pathology and subsequent cognitive decline.
• Findings challenge the notion of homogeneous amyloid spread and highlight the importance of regional deposition patterns.