Importance of tau in cognitive decline as revealed by developmental exposure to lead

Abstract

Previous reports by us have determined that developmental exposure to the heavy metal lead (Pb) resulted in cognitive impairment in aging wildtype mice, and a latent induction in biomarkers associated with both the tau and amyloid pathways. However, the relationship between these two pathways and their correlation to cognitive performance needs to be scrutinized. Here, we investigated the impact of developmental Pb (0.2%) exposure on the amyloid and tau pathways in a transgenic mouse model lacking the tau gene. Cognitive function, and levels of intermediates in the amyloid and tau pathways following postnatal Pb exposure were assessed on young adult and mature transgenic mice. No significant difference in behavioral performance, amyloid precursor protein (APP), or amyloid beta (Aβ) levels was observed in transgenic mice exposed to Pb. Regulators of the tau pathway were impacted by the absence of tau, but no additional change was imparted by Pb exposure. These results revealed that developmental Pb exposure does not cause cognitive decline or change the expression of the amyloid pathway in the absence of tau. The essentiality of tau to mediate cognitive decline by environmental perturbations needs further investigation.

Perinatal Lead (Pb) Exposure and Cortical Neuron-Specific DNA Methylation in Male Mice

“…In adults, Pb exposure is linked to cognitive decline [4], amyloid lateral sclerosis [5], and Parkinson’s disease [6]. Exposure to Pb exerts adverse effects on learning and memory ability in young rats [7,8], mice [9,10], and monkeys [11,12]. Environmental perturbations early in life can affect pathophysiology in adulthood [13,14,15,16,17,18], as described in the Developmental Origins of Health and Disease (DOHaD) paradigm.…”

Comparison of Blood Lead Levels in Patients With Alzheimer’s Disease and Healthy People

“…1 Developmental exposure to the heavy metal Pb has been shown to cause both impaired cognition and a latent induction in biomarkers that are related to the amyloid and tau pathways in aging wildtype mice. [8][9][10][11] Tau and Ab have recently been depicted to be involved in some mutual loop correlation, where actions by one affect the other. This study proposes the necessity of tau for Pb to change both amyloid and tau-related biomarkers.…”

“…Tau is similarly needed for Pb, even though partly, to influence the cognitive function and the AD biomarkers. 8 Lead has been known from ancient times to be an environmental contaminant. After uptake in the human body, the halflife of inorganic Pb is 25 days in blood, 40 days in soft tissues, 7 years in kidneys, and 25 to 32 years in bones.…”

“…Tau is similarly needed for Pb, even though partly, to influence the cognitive function and the AD biomarkers. 8…”

Traumatic Brain Injury and Firearm Use and Risk of Progressive Supranuclear Palsy Among Veterans

“…Additionally, in both rodent and primate models, early exposure to lead was reported to be associated with increased levels of total tau protein and tau mRNA, as well as increased levels of hyperphosphorylated tau and an increased presence of NFTs on brain tissue ( 7 , 8 ). Rodent knock-out models have also confirmed that the tau pathway is required for lead to effect cognitive function ( 20 ).…”