Neocortical neuronal subpopulations labeled by a monoclonal antibody to calbindin exhibit differential vulnerability in Alzheimer's disease.
Numerous studies have demonstrated that specific neuronal subtypes display a differential vulnerability to the pathological process in Alzheimer's disease. Large pyramidal neurons are likely to be highly vulnerable, whereas smaller neurons are more resistant to pathology. Using a monoclonal antibody to the calcium-binding protein calbindin, we observed in the human prefrontal cortex distinct populations of labeled cells. First, a subset of heavily stained interneurons was located in layers II and superficial III and in layers V-VI. Second, a subpopulation of pyramidal neurons in the mid and deep parts of layer III displayed a less intense, punctate staining pattern. The interneurons in the superficial layers were unaffected in the Alzheimer's disease cases. Interestingly, in layers V-VI, there was significant cell loss in the interneuron population, but only in the Alzheimer's disease cases with high neurofibrillary tangle densities. The calbindin-immunoreactive pyramidal neurons of layer III were dramatically affected in the disease. Moreover, there was a strong correlation between the extent of the loss of these cells and neurofibrillary tangle counts. These data suggest that calbindin is present in multiple neuronal subpopulations that exhibit a differential vulnerability in Alzheimer's disease and support the hypothesis that the degenerative process involves specific neuronal subsets with particular anatomical and molecular profiles.
Hof
P R
PR
Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029.
Morrison
J H
JH
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D064026:Calbindins; D002470:Cell Survival; D002540:Cerebral Cortex / Q000166:cytology / Q000473:pathology*; D006801:Humans; D007395:Interneurons / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000473:pathology*; D012016:Reference Values; D064030:S100 Calcium Binding Protein G / Q000032:analysis*
D000911:Antibodies, Monoclonal; D064026:Calbindins; D064030:S100 Calcium Binding Protein G