NIH: Protective Strategies to Reduce Amyloid Related Imaging Abnormalities (ARIA) After Anti-Amyloid Beta Immunotherapy (R01)

Funding Opportunity Number: PAR-24-198

Deadlines: October 4, 2024, November 4, 2024


Goal 1 of the National Plan to Address Alzheimer’s Disease is to prevent and effectively treat Alzheimer’s disease (AD) and Alzheimer’s disease-related dementias (ADRD). ADRD are defined as Frontotemporal Dementia (FTD), Vascular Contributions to Cognitive Impairment and Dementia (VCID), Lewy Body Dementias (LBD), and Multiple Etiology Dementias (MED). Starting in 2012, the National Institute on Aging (NIA) and the National Institute of Neurological Disorders and Stroke (NINDS) have held research summits to assess the needs and set AD/ADRD research implementation milestones. The NINDS ADRD Summit 2022 resulted in ADRD research priorities for advancing the state-of-the-science toward meeting Goal 1 of the National Plan. One priority is to establish and refine experimental models and technologies to identify disease-relevant mechanisms underlying VCID. As beta-amyloid is central to AD pathology, beta-amyloid is being pursued as a therapeutic target, including through passive immunotherapy against beta-amyloid. Because of the translational potential of passive anti-beta-amyloid immunotherapy on the ADRD disease processes, understanding the effect of this therapy on the blood-brain barrier and brain blood vessels in the intact living brain is critically important. In September 2023 NINDS sponsored a workshop to address Amyloid-Related Imaging Abnormalities (ARIA) as a side effect of anti-beta-amyloid immunotherapy with the goals to identify scientific gaps and opportunities (Home – NINDS Anti-Beta and ARIA. Therefore, this NOFO invites basic disease-related applications that use age-appropriate beta-amyloid animal models to understand genetic-, cellular-, and molecular mechanisms of adverse responses that occur at and/or proximal to the BBB due to passive anti-beta-amyloid immunotherapy.

This initiative seeks applications in areas including, but not limited to:

  • Mechanistic studies of the adverse effect of anti-beta amyloid passive immunotherapy on, and proximal to, the blood-brain barrier and brain blood vessels
  • Investigation of protective therapeutic targets and approaches to mitigate the adverse effect of anti-beta amyloid passive immunotherapy.
  • Development of new animal models of cerebral amyloid angiopathy (CAA)/ARIA, including larger species.
  • Mechanistic studies to investigate the relationship between ARIA and its risk factors, such as ApoE4 carrier status, existing microbleeds, overt cerebrovascular disease, neuroinflammation, and existing cerebrovascular risk factors like hypertension and diabetes.
  • Applications proposing neuropathological studies to measure ARIA-related changes in animal models.

Characteristics of Responsive Applications

  • Projects that are primarily focused on ARIA that occurs in response to anti-beta-amyloid passive immunotherapy
  • Applications that include power analyses justifying the proposed research
  • Applications proposing studies that are powered to address age and sex as a biological variable for the proposed hypotheses.

For more information, please see the opportunity website.