ABSTRACT
Measurement of erythrocyte aging parameters in patients with dementia indicates that an Alzheimer-related disturbance of the erythrocyte aging process may not be detectable until in the more advanced stages of the disease. Also, a strong fluctuation in the values of erythrocyte aging parameters, over a period of 15 months, was observed in patients with dementia, but not in age-matched control donors. This fluctuation was independent of the type and stage of dementia, and its cause remains to be elucidated. Such variability hampers the use of erythrocyte aging characteristics for the diagnosis of dementia. On the other hand, the aging-related erythrocyte IgG content may be a sensitive biomarker for disturbed systemic homeostasis in the elderly.
Subject(s)
Dementia/blood , Erythrocyte Aging/physiology , Adult , Aged , Aged, 80 and over , Anion Exchange Protein 1, Erythrocyte/metabolism , Dementia/immunology , Humans , Immunoglobulin G/analysisABSTRACT
Fluorescent microspheres were used to measure antibody-induced capping of leukocyte membrane proteins that are immunologically related to band 3, the anion exchanger of the erythrocyte. The degree of capping was found to increase with donor age. Surface labeling and capping characteristics of cells from healthy, age-matched controls were not different from those from patients with Alzheimer's disease, multi-infarct dementia, and Down's syndrome. Immunoblots, however, indicated increased expression and/or breakdown of band 3-like proteins in leukocytes from patients when compared with young and old control donors. These findings emphasize the possible involvement of band 3-like proteins of nucleated cells in aging and disease.
Subject(s)
Aging/blood , Anion Exchange Protein 1, Erythrocyte/metabolism , Leukocytes/metabolism , Membrane Proteins/blood , Nerve Degeneration/physiology , Adult , Aged , Aged, 80 and over , Alzheimer Disease/blood , Blood Donors , Case-Control Studies , Dementia, Multi-Infarct/blood , Down Syndrome/blood , Humans , Immunoblotting , Middle AgedABSTRACT
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.
Subject(s)
Alzheimer Disease/metabolism , Anion Exchange Protein 1, Erythrocyte/metabolism , Aged , Aged, 80 and over , Alzheimer Disease/immunology , Alzheimer Disease/pathology , Anion Exchange Protein 1, Erythrocyte/immunology , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Electrophoresis, Polyacrylamide Gel , Female , Hippocampus/metabolism , Hippocampus/pathology , Humans , Immunoblotting , Immunohistochemistry , Male , Membrane Proteins/metabolism , Middle Aged , Neurofibrillary Tangles/pathology , Neurons/metabolismABSTRACT
Morphometric analysis of thrombocytes from patients with Alzheimer's disease, from patients with multi-infarct dementia, and from young and age-matched healthy control donors, did not reveal any Alzheimer-related increase in internal membranes. Biochemical analysis showed a reduced cholesterol content of thrombocyte membrane preparations from Alzheimer patients relative to age-matched controls, but not relative to multi-infarct dementia patients. Overall distribution of protein kinase C activity (PKC) between cytosol and membrane, in resting as well as in activated thrombocytes from Alzheimer patients, was similar to that in the control groups. However, both Alzheimer and multi-infarct dementia patients had lower cytosolic levels of basal kinase and PKC activities than age-matched controls, while only Alzheimer patients had lower cytoskeletal PKC activity than controls.
Subject(s)
Alzheimer Disease/metabolism , Blood Platelets/metabolism , Adult , Aged , Aged, 80 and over , Aging/metabolism , Alzheimer Disease/pathology , Blood Platelets/ultrastructure , Cell Membrane/metabolism , Cell Membrane/ultrastructure , Humans , Membrane Lipids/metabolism , Protein Kinase C/metabolismABSTRACT
We measured cytochrome oxidase activity in thrombocytes from patients with senile dementia of the Alzheimer type. We found no decrease in enzyme activity in Alzheimer's disease patients when compared with patients with multi-infarct dementia, with young control donors, and with age-matched control donors.
Subject(s)
Alzheimer Disease/blood , Blood Platelets/enzymology , Electron Transport Complex IV/blood , Adult , Citrate (si)-Synthase/blood , Dementia, Multi-Infarct/blood , HumansABSTRACT
Erythrocytes from patients with Alzheimer's disease show signs of disturbance of the normal cellular aging process. Immunoblotting of erythrocyte membrane proteins from Alzheimer patients reveals increased breakdown of the anion transport protein band 3 in a majority of the cells, similar to what is observed in only a very small cell population during normal aging. These structural changes are accompanied by changes in anion transport characteristics, but the latter partially deviate from those observed during normal aging. The amount of erythrocyte-bound immunoglobulin G, the most direct and relevant parameter of erythrocyte aging, is significantly increased in Alzheimer patients relative to age-matched, healthy donors and to patients with multi-infarct dementia. These data indicate accelerated molecular breakdown of band 3 and premature appearance of senescent cell characteristics in erythrocytes from Alzheimer patients, and support the hypothesis that abnormal cellular aging may be involved in the etiology of the Alzheimer-specific pathology.
