NEUROPATHOLOGIC EVIDENCE THAT THE LEWY BODY VARIANT OF ALZHEIMER-DISEASE REPRESENTS COEXISTENCE OF ALZHEIMER-DISEASE AND IDIOPATHIC PARKINSON-DISEASE

We undertook this study to investigate the neuropathologic relationshi ps among Alzheimer disease (AD), idiopathic Parkinson disease (PD), an d the Lewy body variant of AD (AD/LBV). We retrieved 30 autopsy cases in which Lewy bodies (LB) had been identified in the substantia nigra (SN) in routine hematoxylin-eosin-stained sections. Twenty-two of the cases had a primary clinical diagnosis of dementia and neuropathologic changes of AD; 12 of these demented patients also had clinical parkin sonism. Eight cases had clinical and neuropathologic evidence of PD wi th minimal or no AD neuropathology, though 6 had clinical dementia. Co ntrols consisted of 6 cases of AD without SN LB by hematoxylin-eosin, and 5 neurologically normal aged controls. Paraffin sections of SN, su perior temporal gyrus, and cingulate gyrus from each case were immunos tained with rabbit anti-ubiquitin antiserum, randomized, and analyzed individually by light microscopy, and the density of LB-like profiles in each section were graded. None of 5 nondemented aged controls showe d any neocortical LB, even though 2 had significant numbers of inciden tal SN LB by ubiquitin immunostaining. Of 6 AD cases without SN LB by hematoxylin-eosin, 3 had rare SN LB on ubiquitin stain, 1 of which sho wed rare neocortical Lewy-like profiles. Seven of 8 PD cases showed ne ocortical LB, including the 6 with dementia. Twenty-one of 22 AD cases with SN LB showed ubiquitin-immunoreactive Lewy-like bodies in the ne ocortex that were statistically significantly greater in number than i n either pure PD or pure AD cases. The frequent occurrence of LB in th e neocortex in PD alone suggests that AD/LBV likely represents mixed A D/PD. However, AD neuropathology may favor or promote the formation of neocortical LB in patients who go on to develop mixed AD/PD pathology .