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Distribution of pathological hallmarks and association with post‐mortem MRI cortical thickness in typical and atypical Alzheimer’s disease
Author(s) -
Jonkman Laura E.,
Boon Baayla D.C.,
Frigerio Irene,
Steenwijk Martijn D.,
Preziosa Paolo,
Hoozemans Jeroen J.M.,
Bouwman Femke,
Rozemuller Annemieke J.M.,
Van de Berg Wilma D.J.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.042784
Subject(s) - atrophy , pathology , pathological , medicine , cd68 , neuroimaging , autopsy , immunohistochemistry , psychiatry
Background Alzheimer’s disease (AD) may present with typical amnestic symptoms (70%) as well as atypical non‐amnestic symptoms such as spatial disorientation, aphasia, or behavioural change. This heterogeneity in clinical symptoms is reflected by pathology and neuroimaging, showing different patterns of protein aggregation, inflammation and atrophy. In this study we aimed to assess the within‐subject regional pathological abnormalities and association with MRI cortical atrophy in clinical phenotypes, using a post‐mortem MRI‐pathology pipeline. Method 16 clinically confirmed AD donors, eight typical (4F, 73y ± 9) and eight atypical (3F, 63y ± 11), and 11 non‐neurological donors (6F, 70y ± 7) underwent post‐mortem in‐situ 3T MRI. Upon subsequent autopsy, eight cortical regions were selected for paraffin embedding and Aβ, (p‐)tau and CD68 (clone KP1) immunohistochemistry, which was quantitatively analysed as area %‐load with ImageJ. Freesurfer was used on T1 images to calculate regional cortical thickness. Outcome measures were compared across groups using non‐parametric tests. In a linear mixed model we related regional pathology with cortical thickness, adjusting for age and post‐mortem delay. Result Across all regions, Aβ, (p‐)tau and CD68 load differed between groups; more pathology in (a)typical AD than controls (all p< 0.001), and more (p‐)tau and CD68 in atypical versus typical AD (p<0.001 and p<0.01). Cortical thickness differed between atypical AD and controls (p<0.001), and between atypical and typical AD (p<0.01). Within regions, only comparing clinical phenotypes, no difference in Aβ load or cortical thickness was found, but there was more (p‐)tau in the precuneus (p = 0.04) and more CD68 in the middle (p = 0.03) and superior frontal cortex (p = 0.028) in atypical AD. Across all groups and regions, there was a negative association between cortical thickness and Aβ (p<0.05), (p‐)tau (p<0.001) and CD68 load (p<0.001). Within AD groups, cortical thickness showed a negative association with Aβ for atypical AD, with (p‐)tau for both phenotypes. Within regions, associations with (p‐)tau and CD68 were found for frontal and parietal thickness in (a)typical AD, but none survived Bonferroni correction. Conclusion Our results show regional differences in (p‐)tau, CD68 and cortical thickness between typical and atypical AD, indicating different patterns of pathology and influence on MRI cortical thickness between phenotypes.