Neuroglia in the inferior olivary nucleus during normal aging and Alzheimer's disease

Abstract

Alzheimer disease (AD) is the most common form of adult onset dementia and is characterized by the accumulation of extracellular neuritic plaques (NPs) and intraneuronal neurofibrillary tangles (NFTs), both considered as pathological hallmarks of AD in the disease-specific brain regions [1][2][3] AbstractIt is likely that neuronal loss occurs in certain brain regions in Alzheimer's Disease (AD) without any neurofibrillary pathology. In the human principle inferior olivary nucleus (PO), we have shown that neuronal loss is about 34% (Lasn et al. Journal of Alzheimer Disease, 2001; 3: 159-168), but the fate of the neuroglial cells is unknown. Since the unique network of neurons and neuroglial cells and their cohabitation are essential for normal functioning of CNS, we designed a study to estimate the total number of oligodendrocytes and astrocytes in normally aged and AD brains. The study is based on 10 control and 11 AD post-mortem human brains. An unbiased stereological fractionator method was used. We found significant oligodendroglial cell loss (46%) in AD as compared to control brains, while the total number of astrocytes showed a tendency to decrease. It is likely that the ratio of oligodendroglial cells to neurons remains unchanged even in degenerative states, indicating that oligodendroglial cells parallel neuronal loss. Astroglial cells did not increase in total number, but the ratio to neurons was significantly increased due to the neuronal loss. Using a novel unbiased quantitative method, we were able to describe significant oligodendroglial loss in the PO but the pathogenic mechanism behind remains unknown.

Altered expression of claudin family proteins in Alzheimer's disease and vascular dementia brains

“…To estimate the number of Cl-expressing neurons, astrocytes and oligodendrocytes we applied two-dimension quantification with random systematic sampling and the unbiased optical fractionator method [34], similar to a previous study [35]. In brief, the area of interest was delineated in low magnification (×2.5) using the cursor.…”

Morphometric Analysis of Infant and Adult Medullary Nuclei Through Optical Disector Method

“…In this work, the optical disector method was applied, because of the advantage of eliminating the difficult and time-consuming task of identifying corresponding portions in different physical sections. Most morphometric studies on medullary nuclei, with few exceptions (Tang et al, 2001(Tang et al, /2002Lasn et al, 2006), did not apply the disector or fractionator methods, indicating a not yet complete acquaintance of the importance of the unbiased principles at the basis of such methods. A research group compared analyses of total neuron numbers in MedVe with two-and three-dimensional probes (optical fractionator), finding 18% higher total neuron number with the unbiased method (Lopez et al, 1997;Tang et al, 2001Tang et al, /2002.…”

“…As regards inferior olivary complex, it is not difficult to distinguish its different subnuclei due to clear anatomical borders (Fig. 2C) (Lasn et al, 2006). Haematoxylin-eosin staining usually permitted precise delineation of the medullary nuclei.…”

Still debating a cause and diagnostic criteria for Alzheimer's disease

“…Furthermore, new hypotheses about ␤amyloid toxicity gained some experimental proof, for instance the one regarding the ion channel function [11]. Papers, at least on some of these subjects, were published in Journal of Cellular and Molecular Medicine in the last few years [12][13][14].Development of transgenic mouse models in the past decade allowed researchers to answer specific questions about the disease development, but no model recapitulates the evolution and pathology of AD with fidelity. A fight for better models still goes on.…”

“…Furthermore, new hypotheses about ␤amyloid toxicity gained some experimental proof, for instance the one regarding the ion channel function [11]. Papers, at least on some of these subjects, were published in Journal of Cellular and Molecular Medicine in the last few years [12][13][14].…”