Could “Leuko-araïosis” Be Secondary to Wallerian Degeneration in Alzheimer’s Disease?

Abstract

To determine the possible role of Wallerian degeneration in the pathogenesis of “leuko-araiosis” (LA), we studied brain computer-tomography scans of 98 normotensive and nondiabetic subjects free of cardiac diseases: 32 with Alzheimer’s disease (AD), 36 with Parkinson’s disease (PD), 8 with progressive supranuclear palsy (PSP), and 22 controls. Our study revealed that: (1) in AD, LA scores were greater than in control subjects; (2) in AD, LA was more prominent in posterior periventricular areas, whereas in PD and PSP, LA was more prominent in anterior periventricular areas; (3) in two patients with AD and LA, autopsy revealed diffuse white matter pallor, limited hyaline thickening of small white matter vessels, and mild fibrillary astrocytosis, without any infarction or hypertensive change; and (4) changes were more severe in white matter close to cortical areas with a great density of neurofibrillary tangles but not to cortical areas with a great density of senile plaques. The high LA scores in AD suggested that a factor of LA might be more severe or more widespread in AD than in PD, PSP and normal aging. Differences in the location of LA between the four groups might be due to differences in the location of the gray matter disorder, and might be explained by a Wallerian degeneration phenomenon rather than senile plaques, neurofibrillary tangles or amyloid angiopathy, which have the same location in AD, PD, PSP and normal aging. In addition to previously reported factors, Wallerian degeneration may be another extracerebral predisposing factor of LA.