P3-195: Stereological study on neuroglial cells in the inferior olivary nucleus in normal aging and in Alzheimer disease

Abstract

It is likely that neuronal loss occurs in certain brain regions in Alzheimer Disease (AD) without any neurofibrillary pathology. In the human, principal inferior olivary nucleus (PO) displays no NFTs in sporadic AD cases, but diffuse amyloid–plaques can be seen in affected individuals in relation to Braak staging. We have shown that neuronal loss is about 34% (Lasn, JAD, 2001), but the fate of neuroglial cells is unknown. Since the unique network of neurons and neuroglial cells and their cohabitation are essential for normal functioning in CNS, it is likely that an imbalance in one of these cell groups perturbs this morphofunctional network. The aim of this study is to estimate the total number of oligodendrocytes and astrocytes in human PO to obtain unbiased and comparable results. The study is based on 10 control and 11 post–mortem AD human brains from Huddinge Brain Bank. The sections were stained with cresyl–violet. An unbiased design–based fractionator method was applied. We found significant oligodendroglial cell loss (46%) in AD as compared to control brains, while the total number of astrocytes remains unaffected. It is likely that the ratio of oligodendroglial cells to neurons is unchanged even in degenerative states, indicating that oligodendroglial cells parallel neuronal loss. Astroglial cells did not display astrocytosis, as often reported in other regions affected by neurofibrillary tangles and neuritic plaques. Using novel unbiased quantitative methods, we were able to estimate accurately neuronal and oligodendroglial loss in the PO. It is recognized that the proximity of oligodendroglial cells to neurons plays an important role in neuronal survival. It is still unclear which cell group degenerates first in AD. Some recent data suggest that oligodendrocytes are more vulnerable to amyloid toxicity.