Tau formation is associated with microglial activation in more widespread cortical areas than is amyloid deposition: Neuroimaging / multi‐modal comparisons. (7th December 2020)

• Record Type: Journal Article
• Authors: Leng, Fangda; Hinz, Rainer; Dani, Melanie; Hampshire, Adam; Gentleman, Steve; Brooks, David J; Edison, Paul
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.046045
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Microglial activation has been found surrounding amyloid plaques and neurofibrillary tangles in brains of Alzheimer's subjects . In‐vivo imaging using 11C‐PBR28 (a marker of translocator protein over expressed in activated microglia) has demonstrated significant correlation between both amyloid (18F‐Flutematemol PET) and tau deposition (18F‐AV1451 PET). However, it is not clear whether tau or amyloid predominantly influence microglial activation. Methods: 11C‐PBR28, 18F‐Flutematemol, 18F‐AV1451 PET scans were performed on clinically diagnosed mild cognitive impairment and Alzheimer's dementia patients (n=20). 90‐120 minute summed 18F‐Flutematemol, 80‐100 minute summed 18F‐AV1451 and 60‐90 minute summed 11C‐PBR28 images were created. Tracer uptake in cerebellar grey matter was then sampled and individual image was divided by cerebellar uptake. The images were then smoothed with 6mm FWHM and analysed. Multiple regression analysis was performed using by VoxelStats package with 11C‐PBR28 as dependent variable, and 18F‐Flutematemol, 18F‐AV1451 and age as independent variable. Correction for multiple comparison was applied based on random field theory. Results: In the current model, amyloid deposition was found to contribute to elevated microglial activation in the posterior part of the brain including bilateral temporal, occipital lobe and posterior cingulate. While tau deposition contributed to neuroinflammation in wide‐spread areas covering bilateral frontal, temporal, parietal, occipital lobe and cingulate cortex. Conclusion: In the current model tau deposition had more unique contribution to microglial activation in MCI and AD cohort, suggesting that tau formation has a stronger association with microglial activation which is independent of amyloid deposition.