Nuclear compartmentalization of aluminum in Alzheimer's disease (AD).
Senile dementia of the Alzheimer type (AD) is a fatal encephalopathy of uncertain etiology. Whether the neurotoxin aluminum plays any role in the AD process in unknown. Here we report an increased amount of aluminum in a chromatin subcompartment, the micrococcal nuclease (MN; EC 3.1.31.1) accessible dinucleosome fraction, in neocortical nuclei isolated from 17 control and 21 AD-affected brains. At these MN-accessible loci we also observe an increase in H1 zero linker histone proteins, DNA-binding proteins which are thought to act as regulators of chromatin compaction. These data support the hypothesis that one deleterious effect of aluminum upon nuclear structure in AD-afflicted brain may be to condense brain chromatin nonrandomly through an interaction with H1 zero linker protein and thereby alter the ability of brain DNA to be effectively transcribed.
Lukiw
W J
WJ
Center for Research in Neurodegenerative Disease, University of Toronto, Canada.
Krishnan
B
B
Wong
L
L
Kruck
T P
TP
Bergeron
C
C
Crapper McLachlan
D R
DR
D000328:Adult; D000368:Aged; D000535:Aluminum / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000378:metabolism; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D004247:DNA; D000535:Aluminum