Alzheimer und Blei

[Karlheinz]

Man hat bei 23 Jahre alten Affen, die in der Kindheit vorübergehend einer Bleibelastung ausgesetzt worden waren und zum Zeitpunkt ihres Todes bei guter Gesundheit waren, alzheimertypische Ablagerungen im Gehirn gefunden (im Gegensatz zu einer Kontrollgruppe). Dabei waren die Bleiwerte im Gehirn zuletzt nicht anders als bei der Kontrollgruppe. Man fand Unterschiede in der Genexpression, die darauf hindeuten, dass die Bleiexposition über eine epigenetische Umprogrammierung im Kindesalter zu den Ablagerungen im Alter führten.
Ähnliche Untersuchungen an Ratten waren vorher zu vergleichbaren Ergebnissen gekommen.


J Neurosci. 2008 Jan 2;28(1):3-9.

Alzheimer's disease (AD)-like pathology in aged monkeys after infantile exposure
to environmental metal lead (Pb): evidence for a developmental origin and
environmental link for AD.

Wu J, Basha MR, Brock B, Cox DP, Cardozo-Pelaez F, McPherson CA, Harry J, Rice
DC, Maloney B, Chen D, Lahiri DK, Zawia NH.

Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island,
Kingston, Rhode Island 02881, USA.

The sporadic nature of Alzheimer's disease (AD) argues for an environmental link
that may drive AD pathogenesis; however, the triggering factors and the period of
their action are unknown. Recent studies in rodents have shown that exposure to
lead (Pb) during brain development predetermined the expression and regulation of
the amyloid precursor protein (APP) and its amyloidogenic beta-amyloid (Abeta)
product in old age. Here, we report that the expression of AD-related genes [APP,
BACE1 (beta-site APP cleaving enzyme 1)] as well as their transcriptional
regulator (Sp1) were elevated in aged (23-year-old) monkeys exposed to Pb as
infants. Furthermore, developmental exposure to Pb altered the levels,
characteristics, and intracellular distribution of Abeta staining and amyloid
plaques in the frontal association cortex. These latent effects were accompanied
by a decrease in DNA methyltransferase activity and higher levels of oxidative
damage to DNA, indicating that epigenetic imprinting in early life influenced the
expression of AD-related genes and promoted DNA damage and pathogenesis. These
data suggest that AD pathogenesis is influenced by early life exposures and argue
for both an environmental trigger and a developmental origin of AD.

Volltext: http://www.jneurosci.org/cgi/content/full/28/1/3