Nuclear translocation of NF-kappaB in cholinergic neurons of patients with Alzheimer's disease.
NF-kappaB is a nuclear transcription factor involved in the control of numerous cellular functions, particularly regulation of survival. Translocation from the cytoplasm to the nucleus, an event essential for NK-kappaB activation, could be mediated through the low-affinity nerve growth factor receptor, p75, which has recently been shown to mediate cell death. In the human brain, p75 is exclusively expressed in cholinergic neurons of the basal forebrain. This population degenerates in Alzheimer's disease (AD). To investigate whether p75 could play a role in the vulnerability of these neurons via NF-kappaB activation, we studied the cellular distribution of NF-kappaB in the nucleus basalis of Meynert of four AD patients and four control subjects. The immunostaining observed both in AD patients and control subjects was limited to large, probably cholinergic, neurons. In AD, the proportion of neurons with nuclear NF-kappaB staining was significantly increased, suggesting an association between NF-kappaB functions and the process of cholinergic degeneration in AD.
Boissière
F
F
INSERM U289 and Laboratoire de neuropathologie R. Escourolle, Hôpital de la Salpêtrière, Paris, France.
Hunot
S
S
Faucheux
B
B
Duyckaerts
C
C
Hauw
J J
JJ
Agid
Y
Y
Hirsch
E C
EC
D000109:Acetylcholine / Q000502:physiology*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport / Q000502:physiology; D016022:Case-Control Studies; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D013377:Substantia Innominata / Q000378:metabolism / Q000473:pathology
D016328:NF-kappa B; D000109:Acetylcholine