An immunohistochemical study of the neocortex in Alzheimer's disease
Nisaudah Radenahmad, D. of Anatomy, F. of Sci., PSU.
Pearson, R. C. A., Prof., D. of Biomedical Sci., U. of Sheffield, UK
Neal, J. W., D. of Neuropathology, U. Hospital of Wales, Cardiff, UK
Wilcock, G. K., Prof., Frenchay Hospital, Bristol, UK
Corresponding e-mail : rnisauda@ratree.psu.ac.th
Grant : Government Budget
Published : Research Report
Key words : Alzheimer's disease, frontal cortex, temporal cortex, calcium-binding proteins,
monoclonal anti-neurofilament 200 antibody
To determine the specificity of GABAergic neuronal deficits in Alzheimer's disease, sections of the prefrontal and temporal cortices were immunostained for calbindin, parvalbumin and calretinin. Calbindin immunoreactive neurones consisted of both pyramidal and nonpyramidal cells. In general, pyramidal cells were heavily labelled in prefrontal cortex and lightly labelled in temporal cortex, and located mainly in layer III, whereas nonpyramidal cells were darkly stained and found in all layers, although the majority was found in layers II and III. Parvalbumin immunocytochemistry labelled nonpyramidal cells located in layers II through VI, predominately in layers III-V. Calretinin-immuno-reactive neurones comprised of nonpyramidal cells that were distributed from layer I to VI and in
white matter but that were most numerous in layers II and III. A significant reduction in the total re-lative density of calbindin- and parvalbumin-immunoreactive neurones was observed in Alzheimer group. Calbindin-immunoreactive, particularly pyramidal neurones were more affected than parval-bumin, more severe in temporal than frontal cortex. The density of calretinin-immunoreactive cells
in temporal cortex did not differ between the two groups, suggesting that this deficit may be specific to calbindin- and parvalbumin-containing interneurons. In this study the technique of immunocyto-chemistry was also used to quantify a specific subpopulation of pyramidal cells using monoclonal
anti-neurofilament 200 (phosphorylated and non-phosphorylated; M200) antibody. M200 labelled numerous pyramidal cells located in layers II through VI, but layers III and V contained the greatest number of stained cells. A quantitative determination of pyramidal-positive cells was found not to be significantly reduced in Alzheimer compared with control group. There is evidence to suggest that
the loss of density of calbindin- and parvalbumin-immunoreactive cells in Alzheimer brains may be
due to the characteristic shrinkage of the brain, raising the possibility that the unchanged density of calretinin-immunoreactive cells and pyramidal cells immunoreactive stained by M200 antibody may mask actual loss of these cells. These finding are consistent with the hypothesis that a reduction in
area but not laminar thickness, occuring as a cortical column selective degeneration. This decrease
of calbindin- and parvalbumin-immunoreactive cells parallel with the severity of the neuropathology as reflected by amyloid plaque numbers, amyloid load and total plaque counts in prefrontal cortex suggesting the hypothesis that b-amyloid may lead to destabilize calcium homeostasis and render human cortical neurones vulnerable to excitotoxicity.
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