Investigating the Aβ and tau pathology in autosomal dominant Alzheimer's disease: insights from hybrid PET/MRI and network mapping.

backgroundAutosomal dominant Alzheimer's disease (ADAD) offers a distinct framework to study the preclinical phase of Alzheimer's disease (AD), due to its predictable symptom onset and high penetrance of causative mutations. The study aims to examine the spatial distribution and temporal progression of amyloid-beta (Aβ) and tau pathologies, along with mapping the pathology-functional connectivity network, in asymptomatic ADAD mutation carriers using hybrid positron emission tomography/magnetic resonance imaging (PET/MRI).

methodsParticipants were recruited from the Chinese Familial Alzheimer's Disease Network, comprising 14 asymptomatic ADAD mutation carriers and 20 cognitively normal healthy controls (CN). Aβ deposition was evaluated using

resultsAsymptomatic ADAD carriers demonstrated a significantly greater Aβ burden across the cortex and striatum compared to CN, although tau PET binding did not differ significantly between the groups. Group 2 participants exhibited elevated

conclusionsThis study shows the spatiotemporal progression of Aβ and tau pathologies in preclinical ADAD, supporting the hypothesis that Aβ deposition precedes tau pathology. The rsFC alterations observed associate with tau deposition in asymptomatic carriers indicate early network disruptions. Tau network mapping presents a valuable approach for assessing individualized brain connectivity changes in preclinical AD, mitigating single-subject variability and advancing precision assessment in early-stage AD diagnosis.