Selective cell loss in Edinger-Westphal in asymptomatic elders and Alzheimer's patients

Exaggerated pupillary response to a low concentration of cholinergic antago nists has been suggested as an early marker for Alzheimer's Disease (AD). T o examine the anatomic basis of this phenomenon, we determined possible neu ropathological changes in the Edinger-Westphal (EW) nucleus, a midbrain neu ral center with a significant functional role in the control of pupil size. Stereologically determined neuronal numbers within the EW were counted in individuals with pathologically confirmed AD, control cases with no AD-type pathology, and subjects with AD pathology not meeting diagnostic criteria for AD. The EW of AD patients displayed a marked and striking neuronal loss when compared with controls. In contrast, the number of neurons in the som atic portion of the nucleus of the third cranial nerve (NCNIII) remained in tact. The EW in brains from clinically normal individuals with evidence of early AD-type pathology also displayed a significant and selective loss of neurons. The magnitude of EW neuronal loss in the latter group was smaller than that observed in AD. These findings suggest that pupillary hypersensit ivity in AD may be caused by abnormalities in the EW. Neuronal loss and pat hology within the EW in a subpopulation of clinically silent controls with pathologic findings consistent with early-stage AD constitutes a possible e xplanation for the reported exaggerated pupil response in some normal elder ly subjects. (C) 2001 Elsevier Science Inc. All rights reserved.