alpha B-crystallin is a member of the small heat-shock protein family. Under pathological conditions, the expression of alpha B-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 alpha B-crystallin in the brains of Alzheimer's disease (AD) patients and nondemented controls. An increase in alpha B-crystallin 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 alpha B-crystallin was found in fibrous astrocytes. However, the intensity and range of alpha B-crystallin expression appeared to be limited as compared with the large increase in the number of GFAP-positive astrocytes. This indicates that expression of alpha B-crystallin is not a marker for gliosis in AD. Immunoreactivity to alpha B-crystallin in both astrocytes and microglia was found mainly restricted to areas with senile plaques and neurofibrillary tangles, suggesting the association of alpha B-crystallin with amyloid deposition in AD.

alpha-Crystallin is a major eye lens protein, composed of two types of subunits, alpha A and alpha B. The alpha A subunit is restricted to the lens, but alpha B-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 alpha B-crystallin, the presence of alpha B-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 age-matched control brains weak positive reaction was located in individual oligodendroglia cells and subpial astrocytes. Prominent increase of alpha B-crystallin in pathological glia in CJD may represent a response to stress.

No abstract

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 Alzheimer’s 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 cytoskel-eton 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 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 Alzheimer's 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 Alzheimer's disease-affected regions. We postulate that alterations in membrane-bound, band 3-like molecules may reflect termination of neuronal lifespan in Alzheimer's disease.