K. Renkawek

Expression of αB-crystallin in Alzheimer's disease

AbstractαB-crystallin is a member of the small heatshock protein family. Under pathological conditions, the expression of αB-crystallin increases in proliferating astrocytes, which suggests that this protein, in addition to glial fibrillary acidic protein (GFAP), can be a marker for gliosis in neurodegenerative diseases. Immunoblotting and immunohistochemical methods were used for the detection of αB-crystallin in the brains of Alzheimers disease (AD) patients and nondemented controls. An increase in αB-cyrstallin expression was found in the brains of AD patients. Immunoreaction was present in reactive astrocytes, microglia, and oligodendrocytes, indicating that all types of glia respond to the stress associated with AD pathology. Colocalization of GFAP and αB-crystallin was found in fibrous astrocytes. However, the intensity and range of αB-crystallin expression appeared to be limited as compared with the large increase in the number of GFAP-positive astrocytes. This indicates that expression of αB-crystallin is not a marker for gliosis in AD. Immunoreactivity to αB-crystallin in both astrocytes and microglia was found mainly restricted to areas with senile plaques and neurofibrillary tangles, suggesting the association of αB-crystallin with amyloid deposition in AD.

αB-Crystallin is present in reactive glia in Creutzfeldt-Jakob disease

Summaryα-Crystallin is a major eye lens protein, composed of two types of subunits, αA and αB. The αA subunit is restricted to the lens, but αB-crystallin has recently also been detected in non-lenticular tissues, including the nervous system. With the use of a polyclonal antiserum directed against a synthetic C-terminal peptide of human αB-crystallin, the presence of αB-crystallin could be demonstrated immunohistochemically in astrocytes in the brains of patients with Creutzfeldt-Jakob disease (CJD). Most intensive localization was observed in the spongiotic tissue representing abundant progressively changed astrocytes in CJD. In agematched control brains weak positive reaction was located in individual oligodendroglia cells and subpial astrocytes. Prominent increase of αB-crystallin in pathological glia in CJD may represent a response to stress.

The olfactory bulb in Alzheimer disease: a morphologic study of neuron loss, tangles, and senile plaques in relation to olfaction

SummaryComplete pairs of olfactory bulbs of six Alzheimer disease (AD) patients and of six age-and sex-matched controls were morphologically investigated using a random systematic sampling procedure. The total number of cells and the number of mitral cells were the same for controls and patients, but the volume of the bulb and the number of neurons in the anterior olfactory nucleus (AON) were decreased in AD patients. The loss of AON neurons was limited to the younger AD patients and was very severe (75%). Neurofibrillary tangles (NFT) and senile plaques (SP) were found in controls, but they were more frequent in AD, especially in the younger cases. A new finding was the occurrence of very large numbers of so-called diffuse or “very primitive plaques” with the methenamine-silver stain (MS-SP). NFT and SP were limited to the AON but MS-SP also occurred in other parts of the bulb. The data are discussed in relation to olfaction, and it was concluded that odor identification is processed in central rather than in peripheral olfactory structures.

Galanin-like immunoreactivity within Ch2 neurons in the vertical limb of the diagonal band of Broca in aging and Alzheimer's disease

SummaryThe neuropeptide galanin is known to inhibit the evoked release of acetylcholine in ventral hippocampus of the rat. Co-localization of this peptide with choline acetyltransferase in neurons of the cholinergic septal nuclei has been demonstrated in the rat and non-human primate. The severe deficiency of the cholinergic hippocampal projection system arising mainly from the vertical limb nucleus of the diagonal band of Broca, also referred to as Ch2 region, is a constant finding in Alzheimers disease, a disorder which is neuropathologically characterized by the appearance of senile plaques, neurofibrillary tangles and congophilic angiopathy in neo- and archicortical structures. In the present study for the first time galanin immunoreactivity in the human Ch2 region is morphologically investigated and related to the severity of hippocampal plaques and neurofibrillary tangles in Alzheimers disease. An inverse relationship between decreasing galanin immunoreactivity in the Ch2 region and amounts of senile plaques and neurofibrillary tangles in the hippocampus is indicated. Considering the cholinergic deficiency in Alzheimers disease as a secondary phenomenon to primary cortical and hippocampal lesions, and realizing the inhibitory effect of galanin upon acetylcholine release in hippocampus, this preliminary study suggests that a decreased galanin immunoreactivity in Ch2 in Alzheimers disease reflects a possible negative feedback mechanism to a degenerating cholinergic projection system.

Neuropathological findings in muscle-eye-brain disease (MEB-D)

SummaryCongenital muscular dystrophy (CMD) associated with cerebro-ocular dysplasia named muscle-eye-brain disease (MEB-D) is described in two sisters. Progressive hypotonia, mental retardation and severe visual failure appeared immediately after birth. Pathological examination demonstrated muscular dystrophy, hydrocephalus, type II lissencephaly and defective eye development of foetal origin. The great similarity of the clinical and neuropathological picture of both sisters is in agreement with an autosomal recessive inheritance. Neuropathological distinction between Fukuyama-CMD and MEB-D is a more severe and earlier cerebral developmental defect and the association with ocular dysplasia in MEB-D.

Involvement of neuronal anion exchange proteins in cell death in Alzheimer's disease

Anion exchange (AE) proteins are present in human neurons in the brain. Immunohistochemical data indicate that their apparent expression level increases with age, and especially with degeneration in Alzheimers disease-affected brain areas. The increase in immunoreactivity is probably caused by changes in AE structure that lead to an increased accessibility of hitherto hidden epitopes. These epitopes correspond to regions in the membrane domain that are involved in generation of senescent cell-specific antigen from AE1 in aging erythrocytes. Elucidation of the molecular nature of these changes and the underlying mechanisms, will lead to insight in the processes that govern aging- and degeneration-associated perturbation of membrane integrity. AE-mediated chloride/bicarbonate exchange is a major component in the regulation of intracellular pH. The functional consequences of changes in AE structure may range from acidosis, disturbance of cytoskeleton integrity, and untimely or impaired recognition of cells by components of the immune system, such as microglia. A molecular and physiological description of these changes will establish AE proteins as valuable tools in elucidating the processes of normal aging, and the disturbances in aging-related diseases such as Alzheimers disease.

Proteins immunologically related to erythrocyte anion transporter band 3 are altered in brain areas affected by Alzheimer's disease

Proteins immunologically related to the human erythrocyte anion transporter band 3 are present in neurons of the human neocortex and hippocampus. Immunocytochemical studies show increased band 3 immunoreactivity in neurons in the brains of patients with Alzheimers disease. Immunoblot studies show the presence of band 3-like molecules in brain membrane fractions, and suggest changes in expression and/or processing of band 3-like molecules in Alzheimers disease-affected regions. We postulate that alterations in membrane-bound, band 3-like molecules may reflect termination of neuronal lifespan in Alzheimers disease.

Congenital muscular dystrophy and severe central nervous system atrophy in two siblings

Severe degenerative features of the nervous system of a hitherto unknown kind, associated with a neuromuscular disorder with histopathological features of congenital muscular dystrophy, are reported in two female siblings. The clinical profile was characterized by generalized hypotonia followed by spastic tetraplegia, contractures, polyneuropathy, lack of cognitive development and progressive microcephaly. There was no involvement of the eyes. Neuropathological examination of the brain of one sibling, who died at the age of 30 months, revealed subtotal loss of neurons in the cerebral and cerebellar cortex and in the ventral pons, and secondary loss of myelin in the cerebral and cerebellar subcortical white matter. Sural nerve biopsy in the other sibling, who had a similar neurological affection, showed a lack of large myelinated fibers.

Anion exchange proteins and regulation of intracellular pH in cultured rat astrocytes and neurones.

WE used primary cultures of rat hippocampal tissue to estimate the contribution of anion exchange (AE) proteins to the regulation of intracellular pH in neurones and astrocytes. After induction of acidosis, neonatal rat astrocytes were able to restore the intracellular pH in the absence of extracellular bicarbonate. Neonatal neurones, however, were able to recover from acidosis only when bicarbonate was present in the extra- cellular medium. This recovery was inhibited by inhibition of anion exchange and was independent of the presence of sodium ions. Antibodies against AE proteins reacted predominantly with neurones. These data suggest that neurones in particular are dependent on functional AE proteins for the maintenance of their intracellular pH.

Erythrocyte Band 3-Like Protein Immunoreactivity in the Human Brain Cortex

The immunoreactivity of erythrocyte band 3 (B3-IR)-related protein was estimated on cortex biopsies from the brains of 33 patients varying in age from 14-week-old fetus until 67 years of life. B3-IR was not a feature of embryonic brains. A positive reaction was restricted to neurons. It appeared at early postnatal life, increased sharply until 9 years, and than stayed approximately stable between 17 and 67 years of age. The results indicate that there is a positive relation between the amount of neuronal band 3-like protein and the stage of human brain development.