title: Presenilin-1-immunoreactive neurons are preserved in late-onset Alzheimer's disease.
abstract: Recent studies have suggested that missense mutations in the presenilin-1 gene are causally related to the majority of familial early-onset Alzheimer's disease (AD). To examine the possible involvement of presenilin-1 in late-onset sporadic AD, a quantitative analysis of its distribution in the cerebral cortex of nondemented and AD patients was performed using immunocytochemistry. Stereological analyses revealed that AD brains showed a marked neuronal loss in the CA1 field of the hippocampus and hilus of the dentate gyrus, subiculum, and entorhinal cortex. In these areas, however, the fraction of neurofibrillary tangle (NFT)-free neurons showing presenilin-1 immunoreactivity was increased compared with nondemented controls. In contrast, cortical areas, which displayed no neuronal loss, did not show any significant increase in the fraction of presenilin-1-positive neurons. Moreover, presenilin-1 immunoreactivity was reduced in NFT-containing neurons. Thus, in AD, the fraction of NFT-free neurons that contained presenilin-1 varied from 0.48 to 0.77, whereas the fraction of NFT-containing neurons that were presenilin-1 positive varied from 0.1 to 0.24. Together, these observations indicate that presenilin-1 may have a neuroprotective role and that in AD low cellular expression of this protein may be associated with increased neuronal loss and NFT formation.
authors.affiliation: Department of Psychiatry, University of Geneva School of Medicine, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Giannakopoulos
authors.forename: C
authors.initials: C
authors.lastname: Bouras
authors.forename: E
authors.initials: E
authors.lastname: Kövari
authors.forename: J
authors.initials: J
authors.lastname: Shioi
authors.forename: N
authors.initials: N
authors.lastname: Tezapsidis
authors.forename: P R
authors.initials: PR
authors.lastname: Hof
authors.forename: N K
authors.initials: NK
authors.lastname: Robakis
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D016874:Neurofibrillary Tangles / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D053764:Presenilin-1; D012016:Reference Values; D014018:Tissue Distribution
chemical_list: D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1