# The Role of Copper in Cerebral Amyloid Angiopathy

> **NIH NIH R01** · UNIVERSITY OF RHODE ISLAND · 2020 · $383,750

## Abstract

Vascular cognitive impairment & dementia (VCID) is defined as a form of dementia that is triggered
by damage to cerebral blood vessels or cerebrovascular disease. Cerebral amyloid angiopathy (CAA),
which is accumulation of amyloid ß-protein (Aß) within and along primarily small and medium-sized
arteries and arterioles of the brain and in the cerebral microvasculature, is a common cerebral vascular
condition that can cause VCID in the elderly. Not surprisingly, with the involvement of Aß, CAA is the
most common vascular comorbidity found in the brains of Alzheimer's disease (AD) patients. Although
there is evidence that both parenchymal plaque amyloid and cerebral microvascular amyloid can
contribute to dementia in patients with AD and related disorders, there is growing recognition that the
latter is a potent driver of cognitive impairment. Yet, the reasons as to why cerebral vascular
amyloid forms and its contribution to downstream pathologies and early cognitive impairment
remain unclear.
 Altered copper homeostasis has been considered an important factor in the neurodegenerative
diseases. Earlier findings suggest that copper may play an important role in the formation of amyloid
deposits and in subsequent neuronal dysfunction and cognitive impairment. However, relatively little
is known about the accumulation of copper in cerebral vascular amyloid deposits, which are
associated with early-onset VCID. Thus, the overall hypothesis of our proposal is that copper plays
a role in driving fibrillar amyloid assembly in CAA and that the subsequent accumulation of
copper in the cerebrovascular amyloid deposits promotes downstream pathologies and early-
onset cognitive impairment. In order to test this hypothesis we propose to three specific aims. First,
we will determine if vascular amyloid deposits exhibit high levels of copper compared to parenchymal
amyloid plaques in post mortem human brain tissue samples of AD, sporadic CAA and familial CAA
patients and in transgenic mouse models. Second, we will investigate the effects of copper on Aß fibril
assembly. Third, we will determine the effects of increasing or reducing copper levels on the
development of CAA, downstream pathologies and cognitive impairment in Tg-SwDI mice.
 Currently, there are no effective therapies or reliable biomarkers specifically for CAA. These
deficiencies are complicated by our lack of understanding of the assembly and unique structural
attributes of cerebral vascular amyloid and their distinctive features that lead to CAA formation and
subsequent pathologies. The present proposal, focused on the role of copper in these events, will seek
to fill this critical void in our knowledge and will advance our understanding of the pathogenesis of CAA
and provide insight into the development of novel diagnostic markers and potential therapeutic
interventions for CAA and VCID.

## Key facts

- **NIH application ID:** 9919005
- **Project number:** 5R01NS094201-06
- **Recipient organization:** UNIVERSITY OF RHODE ISLAND
- **Principal Investigator:** LISA M MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,750
- **Award type:** 5
- **Project period:** 2017-10-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919005

## Citation

> US National Institutes of Health, RePORTER application 9919005, The Role of Copper in Cerebral Amyloid Angiopathy (5R01NS094201-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9919005. Licensed CC0.

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