The cellular basis for the relative resistance of parvalbumin and calretinin immunoreactive neocortical neurons to the pathology of Alzheimer's disease.
The vulnerability of nerve cells to the neurofibrillary pathology of Alzheimer's disease (AD) may be determined by the presence within them of certain cytoskeletal proteins. Fluorescence multiple labeling was used to assess the vulnerability of two separate subpopulations of nonpyramidal neurons in the superior frontal gyrus, distinguished by their content of the calcium-binding proteins parvalbumin (PV) and calretinin (CR), to the neuropathology of AD. In AD, counterstaining PV- and CR-labeled sections with thioflavine S demonstrated that the great majority of these cells did not contain neurofibrillary tangles, except for the large CR-immunoreactive neurons in layer I. This latter group of cells was also characterized as containing neurofilament (NF) triplet proteins, whereas other CR-labeled cortical neurons were not immunoreactive for NF. There was also a small AD-related increase in the proportion of PV-labeled cells showing NF protein immunoreactivity (1-9% of the total population in AD cases compared to 0-0.4% in non-AD cases), which likewise may be linked to the susceptibility of a minute proportion (0-0.7%) of these neurons to form neurofibrillary tangles in AD. These data are further evidence that the presence of NF in cortical nerve cells is linked to their vulnerability to the pathological process underlying AD.
Sampson
V L
VL
Division of Pathology, Clinical School, University of Tasmania, Hobart, Australia.
Morrison
J H
JH
Vickers
J C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D052160:Benzothiazoles; D064032:Calbindin 2; D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology*; D003429:Cross Reactions; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000276:immunology; D016501:Neurites / Q000737:chemistry / Q000473:pathology; D016900:Neurofilament Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D010320:Parvalbumins / Q000032:analysis / Q000276:immunology*; D010766:Phosphorylation; D064030:S100 Calcium Binding Protein G / Q000032:analysis / Q000276:immunology*; D013194:Staining and Labeling; D013844:Thiazoles
D052160:Benzothiazoles; C576764:CALB2 protein, human; D064032:Calbindin 2; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D013844:Thiazoles; C009462:thioflavin T