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Neurogenesis Makes a Crucial Contribution to the Neuropathology of Alzheimer’s Disease
- Source :
- Journal of Alzheimer's Disease Reports
- Publication Year :
- 2020
- Publisher :
- IOS Press, 2020.
-
Abstract
- One unexplained feature of Alzheimer’s disease (AD) is that the lateral entorhinal cortex undergoes neurodegeneration before other brain areas. However, this brain region does not have elevated levels of amyloid peptides in comparison with undamaged regions. What is the cause of this special vulnerability of the entorhinal cortex? One special feature of the lateral entorhinal cortex is that it projects to newborn neurons that have undergone adult neurogenesis in the dentate gyrus of the hippocampus. Neurogenesis is abnormal in human AD brains, and modulation of neurogenesis in experimental animals influences the course of AD. This complex process of neurogenesis may expose axon terminals originating from neurons of the entorhinal cortex to a unique combination of molecules that can enhance toxic effects of amyloid. Retrograde degeneration of neurons with axons terminating in the dentate gyrus provides a likely explanation for the spatial patterns of neuronal cell death seen in AD. Specialized astrocytes in the dentate gyrus participate in adult neurogenesis and produce fatty acid binding protein7 (FABP7). These FABP7+ cells undergo an aging-related mitochondrial pathology that likely impairs their functions. This age-related abnormality may contribute to the impairment in neurogenesis seen in aging and Alzheimer’s disease. Also, a compromised function of these astrocytes likely results in local elevations of palmitic acid, iron, copper, and glucose, which all enhance the toxicity of amyloid peptides. Treatments that modulate neurogenesis or diminish the production of these toxic substances may prove more successful than treatments that are solely aimed at reducing the amyloid burden alone.
- Subjects :
- 0301 basic medicine
FABP7
Hippocampus
Neuropathology
Biology
03 medical and health sciences
0302 clinical medicine
Fatty acid binding
medicine
Axon
entorhinal cortex
General Neuroscience
Dentate gyrus
Neurogenesis
Neurodegeneration
astrocytes
Gomori-positive
Hypothesis
Entorhinal cortex
medicine.disease
Psychiatry and Mental health
Clinical Psychology
neurogenesis
030104 developmental biology
medicine.anatomical_structure
copper
Geriatrics and Gerontology
Neuroscience
Alzheimer’s disease
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 25424823
- Volume :
- 4
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's Disease Reports
- Accession number :
- edsair.doi.dedup.....ffd2eef07f85394cd7b979cc1ca32a16