Altered protein composition of isolated human cortical neurons in Alzheimer disease.
To characterize the protein composition of degenerating neurons in Alzheimer disease, enriched fractions of isolated cortical neurons from postmortem Alzheimer brain were compared by ultrastructural and biochemical techniques to neuronal isolates from aged normal controls and from patients with the nonfibrillary degenerative dementia, Huntington disease. Electron microscopy of isolated neurons showed well-preserved organelles, including nuclear membranes, mitochondria, endoplasmic reticulum, ribosomes, and lipofuscin. Abundant paired helical filaments (PHF) were preserved in affected Alzheimer perikarya. In both sporadic and familial Alzheimer disease, sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed marked augmentation of a 20,000 mw protein (P20) in neuronal fractions from affected cortex compared to Huntington disease patients and controls. P20 was commonly increased in hippocampal, temporal, and frontal neurons but not in cortex free of PHF. The augmentation of P20 in Alzheimer disease samples appeared to correlate with the presence of PHF-bearing neurons in the fractions. The increase in P20 in Alzheimer disease was observed in the presence of proteolysis inhibitors, in reverse-sieved samples, and in whole cortical homogenates. Neurofilament proteins, tubulins, and a 50,000 mw protein showed no changes. In Huntington disease, marked augmentation of a 49,000 mw protein was found in striatal but not cortical homogenates. The relationship of these findings to the biochemistry of brain fibrous proteins and to the molecular pathology of Alzheimer disease is discussed.
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D003704:Dementia / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008854:Microscopy, Electron; D008858:Microscopy, Phase-Contrast; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism
D009419:Nerve Tissue Proteins