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Tipping points in neurodegeneration.
- Source :
-
Neuron . Oct2023, Vol. 111 Issue 19, p2954-2968. 15p. - Publication Year :
- 2023
-
Abstract
- In Alzheimer's disease (AD), Aβ deposits form slowly, several decades before further pathological events trigger neurodegeneration and dementia. However, a substantial proportion of affected individuals remains non-demented despite AD pathology, raising questions about the underlying factors that determine the transition to clinical disease. Here, we emphasize the critical function of resilience and resistance factors, which we extend beyond the concept of cognitive reserve to include the glial, immune, and vascular system. We review the evidence and use the metaphor of "tipping points" to illustrate how gradually forming AD neuropathology in the preclinical stage can transition to dementia once adaptive functions of the glial, immune, and vascular system are lost and self-reinforcing pathological cascades are unleashed. Thus, we propose an expanded framework for pathomechanistic research that focuses on tipping points and non-neuronal resilience mechanisms, which may represent previously untapped therapeutic targets in preclinical AD. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ALZHEIMER'S disease
*NEURODEGENERATION
*CARDIOVASCULAR system
*DRUG target
Subjects
Details
- Language :
- English
- ISSN :
- 08966273
- Volume :
- 111
- Issue :
- 19
- Database :
- Academic Search Index
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 172427217
- Full Text :
- https://doi.org/10.1016/j.neuron.2023.05.031