December 30, 2021
PAR-22-093 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional)
PAR-22-094 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R21 Clinical Trial Not Allowed)
National Institute on Aging (NIA)
Etiologic and therapeutic research on dementia has focused either on individual disease syndromes (e.g., Alzheimer’s disease (AD), Lewy Body Dementia (LBD), Frontotemporal Dementia (FTD), Vascular Dementia (VD)) or distinct neurodegenerative processes (e.g., beta-amyloid, HPF-tau, alpha-synuclein, TDP-43, small vessel changes). Aside from descriptive, postmortem neuropathology, different neurodegenerative diseases have generally been investigated in isolation from one another. There are few models for studying whether and how neurodegenerative disease processes relate to one another.
At autopsy, many patients with dementia, particularly older individuals, exhibit multiple neuropathological changes. In addition to tau tangles and beta-amyloid plaques, vascular changes, Lewy bodies, and TDP-43 inclusions are often present. The likelihood of antemortem dementia increases with co-occurring postmortem neuropathological burden. However, despite considerable evidence of interactions between different neuropathological processes, we do not understand how different neurodegenerative illnesses interact or relate to one another.
Co-occurring pathology complicates both pathophysiological investigation and treatment development. For instance, therapies to increase beta-amyloid clearance may be less effective if there is coincident VD or LBD. At the same time, commonalities between neurodegenerative diseases may provide clues to pathophysiological mechanisms. Can multiple neuropathological changes interact to synergistically increase disease burden and worsen cognitive impairment? Could there be common pathways leading to synapse loss and cell death that might become targets for drug development? If either speculation is correct, what molecular, cellular, or organismic processes are involved?
This Notice of Special Interest (NOSI) encourages research to enhance our understanding of how different neurodegenerative diseases interact clinically and physiologically. We need to identify, more precisely, which neurodegenerative process, or processes, are active in individuals. At the same time, we need to better understand how different neurodegenerative diseases resemble and differ from one another at the molecular, cellular, and organismic levels. Cellular and animal models for investigating concurrent neurodegenerative processes need to be developed if we are to answer these questions.
Many neurodegenerative diseases involve aggregation and accumulation of misfolded proteins. Could they be studied as clinical variants of common cellular and molecular biological defects? At the same time, identifying pathophysiologic mechanisms unique to one neuropathologic entity, will be as informative as identifying commonalities.
Examples of issues appropriate to this NOSI include, but are not limited to, the following:
Applications proposing clinical trials on this topic would not be considered a high priority.
Application and Submission Information
This notice applies to due dates on or after March 11, 2022 and subsequent receipt dates through November 13, 2024.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
John Hsiao, M.D.
National Institute on Aging (NIA)