Relationships between arteriosclerosis, cerebral amyloid angiopathy and myelin loss from cerebral cortical white matter in Alzheimer's disease

Pathological relationships between damage to the deep white matter of the cerebral cortex [as evidenced by myelin loss (ML)], cerebral amyloid angiopathy (CAA) and arteriosclerosis (ART) were investigated in the brains of 137 patients with autopsy-confirmed Alzheimer's disease (AD), in order to better understand the causes of white matter damage in AD, and the contribution of this to the pathogenesis of the disorder. All 137 patients had some degree of CAA in one or more brain regions although the occipital cortex was severely affected by CAA more frequently, and consequently mean CAA severity score was significantly greater, than other cortical regions. Eighty-seven patients (63.5%) were affected by ML, with more patients showing ML from occipital cortex than from other cortical regions leading to a significantly higher mean ML severity score in this region. One hundred and twenty-six patients (92%) were affected by ART, although the occipital cortex was not more frequently affected by ART than other cortical areas, the mean ART severity score in occipital cortex was nonetheless significantly greater than that of frontal and temporal cortex. Eighty-seven patients showed both CAA and ML, although there was only a weak correlation between degree of CAA and extent of ML (P = 0.035). Forty-seven patients showed ML and significant ART, 16 patients showed significant ART but no ML, 40 patients showed ML in the absence of significant ART and 34 patients showed neither significant ART nor ML. Overall, and for each of the four brain regions, the extent of ML correlated significantly (P < 0.001) with degree of ART. However, when only those 47 patients with ML and significant ART were considered, much stronger correlations between the extent of ML and the degree of ART were achieved both overall and within each of the four brain regions. The overall ART severity score (and overall scores for each pathological marker of ART) significantly correlated with that of CAA (P < 0.001). Pathological processes leading to white matter damage, in terms of ML at least, in AD are thus likely to be heterogeneous. Many patients suffer ML in association with ART, but in others ML cannot be explained by presence of ART or CAA. In such patients, autoregulatory changes in blood vessels might be responsible for ML. The association between the extent of CAA and ART suggests shared risk factors for each pathological change.