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Amyloid-β, p-tau and reactive microglia are pathological correlates of MRI cortical atrophy in Alzheimer's disease

Authors :
Frederik Barkhof
Jeroen J. M. Hoozemans
Laura E. Jonkman
Annemieke J.M. Rozemuller
John G.J.M. Bol
Baayla D.C. Boon
Chen-Pei Lin
Irene Frigerio
Jos W. R. Twisk
Yvon Galis-de Graaf
Femke H. Bouwman
Paolo Preziosa
Wilma D.J. van de Berg
Anatomy and neurosciences
Pathology
Epidemiology and Data Science
APH - Health Behaviors & Chronic Diseases
APH - Methodology
Radiology and nuclear medicine
Amsterdam Neuroscience - Brain Imaging
Amsterdam Neuroscience - Neuroinfection & -inflammation
Amsterdam Neuroscience - Neurodegeneration
Neurology
Source :
Brain Communications, 3(4):fcab281. Oxford University Press, Frigerio, I, Boon, B D C, Lin, C-P, Graaf, Y G-D, Bol, J, Preziosa, P, Twisk, J, Barkhof, F, Hoozemans, J J M, Bouwman, F H, Rozemuller, A J M, van de Berg, W D J & Jonkman, L E 2021, ' Amyloid-β, p-tau and reactive microglia are pathological correlates of MRI cortical atrophy in Alzheimer's disease ', Brain Communications, vol. 3, no. 4, fcab281 . https://doi.org/10.1093/braincomms/fcab281, Brain Communications
Publication Year :
2021

Abstract

Alzheimer’s disease is characterized by cortical atrophy on MRI and abnormal depositions of amyloid-beta, phosphorylated-tau and inflammation pathologically. However, the relative contribution of these pathological hallmarks to cortical atrophy, a widely used MRI biomarker in Alzheimer’s disease, is yet to be defined. Therefore, the aim of this study was to identify the histopathological correlates of MRI cortical atrophy in Alzheimer’s disease donors, and its typical amnestic and atypical non-amnestic phenotypes. Nineteen Alzheimer’s disease (of which 10 typical and 9 atypical) and 10 non-neurological control brain donors underwent post-mortem in situ 3T 3D-T1, from which cortical thickness was calculated with Freesurfer. Upon subsequent autopsy, 12 cortical brain regions from the right hemisphere and 9 from the left hemisphere were dissected and immunostained for amyloid-beta, phosphorylated-tau and reactive microglia, and percentage area load was calculated for each marker using ImageJ. In addition, post-mortem MRI was compared to ante-mortem MRI of the same Alzheimer’s disease donors when available. MRI-pathology associations were assessed using linear mixed models. Higher amyloid-beta load weakly correlated with higher cortical thickness globally (r = 0.22, P = 0.022). Phosphorylated-tau strongly correlated with cortical atrophy in temporal and frontal regions (−0.76 < r < −1.00, all P < 0.05). Reactive microglia load strongly correlated with cortical atrophy in the parietal region (r = −0.94, P < 0.001). Moreover, post-mortem MRI scans showed high concordance with ante-mortem scans acquired<br />Frigerio et al. report that in Alzheimer’s disease, amyloid-beta, phosphorylated-tau and reactive microglia load measured with immunohistochemistry, are important correlates of MRI cortical atrophy, acquired both ante-mortem in vivo and post-mortem in situ. In summary, distinct histopathological markers differently correlate with cortical atrophy, highlighting their different roles in the neurodegeneration process.<br />Graphical Abstract Graphical Abstract

Details

Language :
English
ISSN :
26321297
Database :
OpenAIRE
Journal :
Brain Communications, 3(4):fcab281. Oxford University Press, Frigerio, I, Boon, B D C, Lin, C-P, Graaf, Y G-D, Bol, J, Preziosa, P, Twisk, J, Barkhof, F, Hoozemans, J J M, Bouwman, F H, Rozemuller, A J M, van de Berg, W D J & Jonkman, L E 2021, ' Amyloid-β, p-tau and reactive microglia are pathological correlates of MRI cortical atrophy in Alzheimer's disease ', Brain Communications, vol. 3, no. 4, fcab281 . https://doi.org/10.1093/braincomms/fcab281, Brain Communications
Accession number :
edsair.doi.dedup.....1aa96e9e7f3dae45998d684c3acfb2ca
Full Text :
https://doi.org/10.1093/braincomms/fcab281