Cortical tau load is associated with white matter hyperintensities

• DOI: 10.1186/s40478-015-0240-0
• Publication Date: 2015-09-29T20:36:02Z
• Authors: Kirsty E. McAleese; Michael Firbank; Madhurima Dey; Sean J. Colloby; Lauren Walker; Mary Johnson; Joshua R. Beverley; John Paul Taylor; Alan J. Thomas; John T. O’Brien; Johannes Attems
• Keywords: Aged, 80 and over; Cerebral Cortex; Male; Amyloid beta-Peptides; Research; tau Proteins; Magnetic Resonance Imaging; Severity of Illness Index; Statistics, Nonparametric; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Alzheimer Disease; Leukoencephalopathies; Postmortem Changes; Humans; Female; Aged

Cerebral white matter lesions (WML), visualized as hyperintensities (WMH) on T2-weighted MRI, encompass structural damage and loss of integrity the cerebral (WM) are commonly assumed to be associated with small vessel disease (SVD). However, it has been suggested that WM may also result degenerative axonal is secondary cortical Alzheimer's (AD) pathologies i.e., hyperphosphorylated tau (HPτ) amyloid-beta (Aβ). Here we investigate influence HPτ, Aβ SVD WMH severity. 36 human post-mortem right fixed hemispheres (mean age 84.4 ± 7.7 years; male: 16, female: 20) containing varying amounts AD-pathology (AD: 23, controls: 13) underwent T2- weighted MRI assessed according related change scale (ARWMC). After dissection, using tissue samples from frontal, temporal, parietal occipital regions hemisphere, quantitatively HPτ pathology burden by measuring percentage area covered AT8 immunoreactivity (HPτ-IR) 4G8 (Aβ-IR), severity calculating sclerotic index (SI) arteries/arterioles. HPτ-IR, Aβ-IR, SI were compared ARWMC scores. Aβ-IR scores all significantly higher in AD cases controls, while values similar between groups. correlated various regions, however, linear regression revealed only HPτ-IR was a significant independent predictor have shown increasing independently predicted indicating its potentially important role pathogenesis damage. Moreover, our findings suggest patients presence indicate AD-associated rather than SVD. Further studies warranted elucidate pathological processes lead clarify if serve general biomarker for pathology.