Relationship between tau, neuroinflammation and atrophy in Alzheimer's disease: The NIMROD study

摘要: Abstract In addition to beta-amyloid accumulation, misfolded tau and activated microglia are also present in Alzheimer's disease (AD). It is important study the relationship amongst these pathologies vivo their effects on cognitive deficits for developing effective trails future therapeutic or preventive strategies AD. To investigate relationships different AD, particular how they interact resulting impairments, we conducted a of sixty-six subjects (15 24 Mild Cognitive Impairment (MCI) 27 similarly aged healthy controls), who underwent standardised clinical neuropsychological assessments followed by dynamic PET using [18F]AV1451 (tau) [11C]PK11195 (activated microglia) multimodal 3T MRI. MCI patients [11C]PIB (beta-amyloid) PET. We compared regional binding grey matter atrophy amyloid positive controls, as well spatial distribution across brain areas. applied mediation analysis infer direct indirect tau, neuroinflammation functioning. found increased with strong overlap AD related biomarkers suggesting them interacting each other. demonstrated that both ([18F]AV1451) ([11C]PK11195) have significant cognition however were fully mediated atrophy. No effect between respect cognition. conclusion, not only spatially overlapped activity but mediate affecting impairments. The enabled data fusion multiple imaging modalities (PET MRI) tracers. Our results implications trials targeting inflammation,