Increased levels of alpha-1-antichymotrypsin in brains of patients with Alzheimer's disease correlate with activated astrocytes and are affected by APOE 4 genotype.
Levels of alpha-1-antichymotrypsin (ACT) were higher in brain homogenates of patients with Alzheimer's disease (AD) than controls. Brain tissues from the same patients and controls were immunostained with antibodies specific for microglia or astrocytes, the leukocyte common antigen (CD45) and glial fibrillary acidic protein (GFAP), respectively. Both activated CD45 and GFAP cells were increased in AD. Astroglia were divided into scattered (CD45sc) and clustered microglia (CD45cl) or scattered (GFAPsc) and clustered astrocytes (GFAPcl). Clustered cells were defined according their tendency to form focal aggregates. CD45cl and GFAPcl cells were present only in AD brain, while CD45sc and GFAPsc positive cells were present either in AD or control brains, with AD brains showing increased numbers of both cell types. A positive correlation between brain ACT levels and the number of GFAPsc positive cells was present in AD. AD patients with APOE 4 allele showed increased levels of ACT and increased CD45sc positive cells. Elevated ACT levels in the brain of AD patients could be interpreted as a metabolic response of astrocytes which might modulate the potentially deleterious activation of microglia cells.
Dipartimento di Patologia Sperimentale, University of Bologna, Italy. licastro@alma.unibo.it
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Licastro
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Mallory
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Hansen
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Masliah
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002449:Cell Aggregation / Q000502:physiology; D004396:Coloring Agents; D005260:Female; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D010641:Phenotype; D012044:Regression Analysis; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004396:Coloring Agents; D005904:Glial Fibrillary Acidic Protein; D000514:alpha 1-Antichymotrypsin; D017493:Leukocyte Common Antigens