Early-life Exposure to Lead Causes Alzheimer’s Like Changes in Older Monkeys

Jean Harry, Ph.D., NIEHS, and Nasser H. Zawia, Ph.D.
University of Rhode Island
NIEHS Grant R21ES013022

Alzheimer’s-like symptoms were seen in a group of older long-tailed macaque monkeys given low levels of lead in infant formula during the first 400 days of life. The findings suggest that Alzheimer’s disease is influenced by early-life exposures to environmental triggers.  NIEHS grantees and intramural scientists collaborated on the study.

The monkeys’ blood lead levels at the end of the exposure period were in the range of 19-26 micrograms/deciliter and resembled the levels seen in many inner city children. After they had reached adulthood, their blood lead levels were the same as the control group indicating that any significant exposure was confined to the developmental and adolescent periods. No health problems were found in any of the monkeys during the 23-year study.

The researchers discovered amyloid protein plaques differences and changes in gene expression in the lead-exposed monkeys.  All of the adult monkeys were found to have amyloid plaques, but the lead-exposed group’s plaques were more numerous and more dense.  Expression of Alzheimer’s specific genes (APP and BACE1) was elevated in the lead-exposed monkeys. These effects were accompanied by higher levels of DNA oxidation and decreased DNA methyl-transferase activity suggesting epigenetic influences on the expression of the Alzheimer’s disease-related genes. 

Citation: 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.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.