INCREASED LEVELS OF ALPHA-1-ANTICHYMOTRYPSIN IN BRAINS OF PATIENTS WITH ALZHEIMERS-DISEASE CORRELATE WITH ACTIVATED ASTROCYTES AND ARE AFFECTED BY APOE 4 GENOTYPE

Levels of alpha-1-antichymotrypsin (ACT) were higher in brain homogena tes of patients with Alzheimer's disease (AD) than controls. Brain tis sues from the same patients and controls were immunostained with antib odies specific for microglia or astrocytes, the leukocyte common antig en (CD45) and glial fibrillary acidic protein (GFAP), respectively. Bo th activated CD45 and GFAP cells were increased in AD. Astroglia were divided into scattered (CD45sc) and clustered microglia (CD45cl) or sc attered (GFAPsc) and clustered astrocytes (GFAPcl). Clustered cells we re defined according their tendency to form focal aggregates. CD45cl a nd GFAPcl cells were present only in AD brain, while CD45sc and GFAPsc positive cells were present either in AD or control brains, with AD b rains showing increased numbers of both cell types. A positive correla tion between brain ACT levels and the number of GFAPsc positive cells was present in AD. AD patients with APOE 4 allele showed increased lev els 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 activa tion of microglia cells. (C) 1998 Elsevier Science B.V. All rights res erved.