# Lead Exposure and Beta-Amyloid Transport by Brain Barriers

> **NIH NIH R01** · PURDUE UNIVERSITY · 2020 · $131,997

## Abstract

Project Summary /Abstract
Accumulation of beta-amyloid (AP) in brain extracellular parenchyma and fluid is the key event
in the amyloid cascade leading to neuronal cell damage in the etiology of Alzheimer's disease
(AD), The blood-brain barrier (BBB) and the blood-CSF barrier (BCB) play an important role in
maintaining the homeostasis of AP in brain extracellular milieu. Pb toxicity on brain barriers
may affect the critical processes in brain barrier systems that regulate AP transport and
metabolism Thus, the central hypothesis is that exposure to Pb damages the brain barrier
systems, which compromises the clearance and eventually increases the leakage of AP at the
BBB and BCB, facilitates the physiochemical reactions between AP and Pb ions, ultimately
leading to an increased formation of amyloid plaques in both brains and blood vessels. To test
this hypothesis, we have designed three specific aims. In aim 1, we will use the state-of-the-art
dynamic contrast-enhanced computed tomography (DCE-CT) to quantify the real-time brain
regional blood flow, blood volume, and BBB permeability before and after Pb exposure in TgAPP
mice develop brain amyloid plaques as well as WT mice. We will also characterize the shift
of fibril AP deposits from the brain's capillary vessels to its parenchyma as a result of Pb
exposure in a dose-time dependent fashion. We will focus on expressions of two AP
transporters, i.e., lipoprotein receptor protein-1 (LRPl) and advanced glycation endproducts
(RAGE), in the BBB treated with Pb. Aim 2 will focus on the role of RAGE and LRP- lin mediating
AP transport by mainly the BCB. In Aim 3, we will use synchrotron X-ray fluorescence (XRF)
imaging technique coupled with immunohistochemistry to co-localize Pb with amyloid
aggregates and K X-ray fluorescence (KXRF) technique quantify real-time Pb concentrations in
bone (PbBn) to establish the association between PbBn and amyloid in brain and blood vessels
after Pb exposure at different doses and time. These studies will establish a novel concept that
the brain barriers play a key role in regulating Pb-induced AP oligomers and plaques in brain
and blood vessels by investigating the relationship between Pb exposure and permeability
changes of brain barriers to AP fluxes and provide clues as to whether chronic Pb exposure and
changes in cerebral vascular permeability contribute to AD pathogenesis and development.

## Key facts

- **NIH application ID:** 10038617
- **Project number:** 3R01ES027078-04S1
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** YANSHENG DU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $131,997
- **Award type:** 3
- **Project period:** 2017-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038617

## Citation

> US National Institutes of Health, RePORTER application 10038617, Lead Exposure and Beta-Amyloid Transport by Brain Barriers (3R01ES027078-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10038617. Licensed CC0.

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