Altered apolipoprotein D expression in the brain of patients with Alzheimer disease

The etiology of late-onset Alzheimer disease is poorly understood. Predispo sing factors such as the apolipoprotein E4 allele, as well as protective fa ctors (e.g., antioxidants) have been proposed to play a role in the disease 's process. A search for predisposing factors contributing to sporadic late -onset Alzheimer disease was initiated using the differential display techn ique. RNA expression profiles of the entorhinal cortex and the cerebellum o f Alzheimer-diseased and normal patients were compared. The entorhinal cort ex is the first brain region to accumulate neurofibrillary tangles during d isease progression, whereas the cerebellum is spared. In the Alzheimer case s of this study, one signal showing preferential expression in the entorhin al cortex corresponded to the apolipoprotein D gene. This preferential expr ession might be genuine at the RNA level as suggested by the in situ hybrid ization method used. In addition, immunohistochemical experiments showed hi gher percentages of Apolipoprotein D reactive pyramidal neurons in the ento rhinal cortex and region I of Ammon's horn in diseased patients. This incre ase correlated with the number of neurofibrillary tangles in Alzheimer as w ell as in normal patients. Colocalization of Apolipoprotein D proteins and neurofibrillary tangles in the same neuron was rare. Thus, these results su ggest that in Alzheimer disease and aging, apolipoprotein D gene expression is increased in stressed cortical neurons before they possibly accumulate neurofibrillary tangles. (C) 2001 Wiley-Liss, Inc.