Neuroinflammation is associated with the rising of early Alzheimer's disease pathology in amyloid‐negative elderly.

Background: Amyloid‐β (Aβ) and tau are the two well‐recognised pathological hallmarks of Alzheimer's disease (AD). In the recent decades, increasing evidence supports neuroinflammation as one of the earliest pathomechanistic alterations throughout the AD continuum. However, little is known about the spatial and temporal patterns of neuroinflammatory processes based on AD pathological status. Furthermore, it also remains elusive how longitudinal change of neuroinflammation affects cerebral amyloid and tau load in the trajectory of AD. Method: We examined a total number of 122 subjects (mean age= 65.6 years, 66.4% women, 33.1% APOEɛ4 carriers) from the TRIAD cohort at McGill University Research Centre for Studies in Aging. Neuroinflammation, cerebral Aβ load and tau deposition were assessed with positron emission tomography (PET) radiotracers [11C]PBR28, [18F]AZD4694 ([18F]NAV4694) and [18F]MK6240 respectively. Amyloid‐β positivity was determined by a cortical composite [18F]NAV4694 SUVR threshold of 1.55, based on previously published method. Voxelwise analyses were performed to evaluate the relationships between cerebral amyloid load and neuroinflammation. A subgroup of 42 subjects who had underwent two‐year follow‐up PET scans were used to study how the longitudinal change of neuroinflammation affects other AD hallmarks. Result: At early stages of amyloid pathology, we found a positive linear relationship between neuroinflammation and amyloid load. Voxelwise analyses also revealed a stronger association between amyloid and neuroinflammation among the Aβ‐negative subjects. Longitudinally, the increase of neuroinflammation was linked to the accumulation of cerebral amyloid and tau in Aβ‐negative subjects. Conclusion: Neuroinflammation was associated with amyloid at early stages of amyloid pathology. In addition, elevation of neuroinflammation was associated with the increase of amyloid and tau accumulation in Aβ‐negative subjects. [ABSTRACT FROM AUTHOR]