Fig. 2

A series of images for three separate cases indicating normal-appearing white matter and the similarity of white matter changes with differing pathogenesis in the deep white matter of the parietal lobe (Brodman area 39/40), as seen on both T2-weighted magnetic resonance imaging (MRI) and on histology. (A–Aiv) Normal-aged control brain with no obvious white matter changes or small vessel disease (SVD), and no Alzheimer’s disease (AD)-related pathology: (A) post-mortem T2-weighted MRI scan of normal-appearing white matter; (Ai, Aii) corresponding histological magnified image of normal-appearing white matter and a normal white matter artery (Aii); (Aiv) overlying cortex with no hyperphosphorylated tau (HPτ) pathology. (B–Biv) Normal-aged case that exhibited severe white matter hyperintensities (WMHs)/lesions with SVD but no AD pathology: (B) post-mortem T2-weighted MRI scan indicating confluent WMH; (Bi) corresponding histological magnified image of white matter lesion indicated by widespread pallor of the central white matter with typical sparing of the subcortical U-fibres (arrow); (Bii) higher magnification of white matter lesion exhibiting severe rarefaction, that is, myelin and axonal loss; (Biii) white matter arterioles from white matter lesion area exhibiting arteriolosclerosis with hyalinisation (arrows) of vessel walls; (Biv) overlying cortex with no HPτ pathology. In this case, one may speculate SVD-related hypoperfusion was the primary cause of white matter changes. (C–Civ) AD brain exhibiting severe WMHs/lesions and no obvious SVD: (C) post-mortem T2-weighted MRI scan indicating confluent white WMH; (Ci) white matter lesion with severe white matter pallor; (Cii) magnified image of severe white matter rarefaction; (Ciii) white matter arteriole with enlarged perivascular space but no SVD-related fibrosis or hyalinisation; (Civ, overlying parietal cortex exhibiting severe HPτ pathology. In this case, one may speculate white matter changes were the result of degenerative myelin and axonal loss as a result of grey matter atrophy in the overlying cortex or via protease-mediated degradation, activated by AD pathology-related axonal transport dysfunction. MRI scans captured in sagittal plane. Microphotoimages captured from serial sections. Histological stain Luxol fast blue was used for images Ai–ii, Bi–ii and Ci–ii; hematoxylin and eosin stain was used for Aiii, Biii and Ciii. Immunohistochemistry with the AT8 antibody was performed in Aiv, Biv and Civ. Scale bars represent 1000 μm in images A, B and C and 20 μm in images Ai–iii, Bi–iii and Ci–iii