# The blood-brain barrier and Alzheimer pathology

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $662,492

## Abstract

Project Abstract
 Dysfunction of the vascular blood-brain barrier (BBB) and cerebrovascular leakiness are
present during aging and in Alzheimer's disease (AD) and are associated with the onset of
preclinical mild-cognitive impairment. Based on recent discoveries we have defined a highly
explanatory biological pathway that directly causes neural dysfunction and cognitive impairment
following BBB dysfunction. While it is intuitive that loss of function of the fundamental vascular
interface that protects the brain would be expected to cause neurological complications that
may contribute to AD, previously there has not been a clearly defined mechanism linking BBB
dysfunction to AD pathology. Existing data in humans suffer from limitations related to possible
regional differences in BBB leakage and the temporal characteristics of BBB disruption
particularly in relation to the deposition of the two proteins that have been implicated in AD
pathogenesis, -amyloid (A) and pathological aggregates of tau.
 Very few studies have examined how these pathological proteins are related to BBB
disruption, and there is no exploration of the four crucially different scenarios: (1) that there is no
relationship between AD pathological proteins and BBB disruption (2) that BBB disruption leads
to increased accumulation of these proteins or (3) that increased accumulation of these proteins
leads to BBB disruption. (4) AD protein pathologies and BBB disruption form a positive feedback
loop that originates with either and are related via the exacerbation of transmission/spread of
protein pathologies by conditions created by BBB disruption.
 In this study we will combine descriptive longitudinal data in cognitively normal humans
using PET scanning to obtain tau and A measurements and dynamic contrast enhanced
magnetic resonance imaging (DCE-MRI) to obtain BBB measurements, with studies in
transgenic mouse models of AD where we will manipulate the BBB. Together these studies will
probe mechanisms of AD pathogenesis in mouse models that enable dissecting the individual
contributions of BBB disruption, amyloid and tau by manipulating each separately, and human
studies that translate these basic findings to observations in the human situation of aging and
preclinical AD.

## Key facts

- **NIH application ID:** 10800246
- **Project number:** 1R01AG080043-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** William J. Jagust
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $662,492
- **Award type:** 1
- **Project period:** 2023-09-30 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800246

## Citation

> US National Institutes of Health, RePORTER application 10800246, The blood-brain barrier and Alzheimer pathology (1R01AG080043-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10800246. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*