Inability to detect beta-amyloid protein precursor mRNA in Alzheimer plaque-associated microglia.
A close association between Alzheimer senile plaques and microglia (the resident mononuclear phagocytic system cells of the brain) is well documented. To determine whether microglia contain detectable beta-amyloid protein precursor (beta-APP) mRNA, the present study combined immunocytochemistry (LN3 antibody to label microglia) with in situ hybridization (full-length cRNA probe to detect all forms of beta-APP mRNA). We report that immunolabeled microglia, including those clustered around senile plaques, generally lack detectable beta-APP mRNA--suggesting that microglia are not synthesizing the plaque-associated amyloid. The possibility that, analogous to the process in other forms of amyloidosis, the resident mononuclear phagocytic cells ingest an amyloidogenic precursor and secrete amyloid was not examined. Recent demonstrations of interactions between immune-related factors and Alzheimer lesions suggest that beta-APP and its breakdown products, along with microglia and their secretory products, may work synergistically in an AD pathogenetic cascade.
Scott
S A
SA
Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033.
Johnson
S A
SA
Zarow
C
C
Perlmutter
L S
LS
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000473:pathology; D009457:Neuroglia / Q000737:chemistry* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger