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

Summary

To determine the possible role of Wallerian degeneration in the pathogenesis of “leuko-araïosis” (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.

Symmetrical periventricular and subcortical white matter lucencies have been reported in healthy elderly subjects, using CT scans (Steingart et al. 1987 a; Rezek et al. 1987). They are correlated to age, mean systolic blood pressure, and previous cardiovascular diseases, but not to sex (Steingart et al. 1987a; Rezek et al. 1987; Inzitari et al. 1987; Kinkel et al. 1985). In demented patients they are correlated to the severity of the dementia and to the presence of neurological abnormalities (Steingart et al. 1987b). They are more frequent in multi-infarct dementia than in Alzheimer’s disease (AD) (Steingart et al. 1987 b; Gupta et al. 1988; Aharon-Peretz et al. 1988).

In 1987 Hachinski et al. called these periventricular white matter lucencies, whose clinical significance and pathogenesis are not clearly established, “leukoaraïosis” (LA). In hypertensive subjects LA is usually attributed to subcortical vascular changes and the terms “subcortical arteriosclerotic encephalopathy” (Kinkel et al. 1985; Loizou et al. 1981) or “Binswanger’s disease” (Aharon-Peretz et al. 1988; De Reuck et al. 1980) are commonly applied. Nevertheless, Rezek et al. (1987) in a study of five patients with LA and definite AD found only diffuse white matter pallor, mild fibrillary astrocytosis and hyaline mural thickening of small cerebral arteries, without any hypertensive vascular change or infarction.

The current study was undertaken to determine the possible role of Wallerian degeneration in the pathogenesis of LA in AD.

This study was supported by grants from INSERM (grant CAR 489016), University Lille II, and the Société de Médecine du Nord.