title: Enhanced taupathy and AD-like pathology in aged primate brains decades after infantile exposure to lead (Pb).
abstract: Late Onset Alzheimer Disease (LOAD) constitutes the majority of AD cases (∼90%). Amyloidosis and tau pathology, which are present in AD brains, appear to be sporadic in nature. We have previously shown that infantile lead (Pb) exposure is associated with a change in the expression and regulation of the amyloid precursor protein (APP) and its beta amyloid (Aβ) products in old age. Here we report that infantile Pb exposure elevated the mRNA and protein levels of tau as well as its transcriptional regulators namely specificity protein 1 and 3 (Sp1 and Sp3) in aged primates. These changes were also accompanied by an enhancement in site-specific tau phosphorylation as well as an increase in the mRNA and protein levels of cyclin dependent kinase 5 (cdk5). There was also a change in the protein ratio of p35/p25 with more Serine/Threonine phosphatase activity present in aged primates exposed to Pb as infants. These molecular alterations favored abundant tau phosphorylation and immunoreactivity in the frontal cortex of aged primates with prior Pb exposure. These findings provide more evidence that neurodegenerative diseases may be products of environmental influences that occur during the development.
authors: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
authors: Syed Waseem
authors: SW
authors: Bihaqi
authors: Nasser H
authors: NH
authors: Zawia
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D015331:Cohort Studies; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007854:Lead / Q000633:toxicity; D020263:Lead Poisoning, Nervous System / Q000150:complications* / Q000473:pathology*; D008252:Macaca fascicularis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D009419:Nerve Tissue Proteins; D016875:tau Proteins; D007854:Lead; D051360:Cyclin-Dependent Kinase 5
keywords: Aging; Alzheimer's disease; Hyperphosphorylation; Lead; Tau protein; cdk5
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