Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 132, Issue 10, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI158453
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Funding
- Alzheimer's Drug Discovery Foundation [GC-201908-2019443]
- Alzheimer's Association Part the Cloud + Bill Gates Partnership [PTCG20-695184]
- National Institute on Aging [R21AG068731, P30AG066546]
- Center for Biomedical Neurosciences at the University of Texas Health Science Center at San Antonio
- Coordinating Center for Claude D. Pepper Older Americans Independence Centers [U24AG059624]
- NIH Clinical and Translational Science Award [TL1 TR0026]
- Texas Alzheimer's Research and Care Consortium
- San Antonio Claude D. Pepper Older Americans Independence Center
- Institute for Integration of Medicine Science
- National Institute on Aging
- Alzheimer's Association Part the Cloud + Bill Gates Partnership
- Alzheimer's Drug Discovery Foundation
- Cure Alzheimer's Fund
- Charleston Conference on Alzheimer's Disease
- Older Americans Independence Center National Coordinating Center
- National Institute of Neurological Disorders and Stroke
- North Carolina Diabetes Research Center
- US Department of Veterans Affairs
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This review provides an overview of the development of ADRD and the relationship between age-related cognitive decline and neurodegenerative changes, highlighting aging processes differentially regulated in neurodegenerative disease. Targeting fundamental processes underlying biological aging may represent a novel avenue to attenuate the development of ADRD.
Alzheimer???s disease and related dementias (ADRD) are among the top contributors to disability and mortality in later life. As with many chronic conditions, aging is the single most influential factor in the development of ADRD. Even among older adults who remain free of dementia throughout their lives, cognitive decline and neurodegenerative changes are appreciable with advancing age, suggesting shared pathophysiological mechanisms. In this Review, we provide an overview of changes in cognition, brain morphology, and neuropathological protein accumulation across the lifespan in humans, with complementary and mechanistic evidence from animal models. Next, we highlight selected aging processes that are differentially regulated in neurodegenerative disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular dysfunction, inflammation, and lipid dysregulation. We summarize research across clinical and translational studies to link biological aging processes to underlying ADRD pathogenesis. Targeting fundamental processes underlying biological aging may represent a yet relatively unexplored avenue to attenuate both age-related cognitive decline and ADRD. Collaboration across the fields of geroscience and neuroscience, coupled with the development of new translational animal models that more closely align with human disease processes, is necessary to advance novel therapeutic discovery in this realm.
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