Opposing Roles of apolipoprotein E in aging and neurodegeneration
| Autor: | Tara L. Spires-Jones, Claudia Cannavo, Bradley T. Hyman, Taylie Sargent, Rebecca A. Betensky, Jacob Aaron Klickstein, Kishore V. Kuchibhotla, Eloise Hudry, Alona Muzikansky, Lauren Wrobleski, Allyson D. Roe, David Urick, Steven S. Hou, Rosemary J. Jackson, Sheetal Gandhi |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Aging Amyloid Health Toxicology and Mutagenesis Mice Transgenic Plaque Amyloid Plant Science Biochemistry Genetics and Molecular Biology (miscellaneous) Neuroprotection 03 medical and health sciences Amyloid beta-Protein Precursor Mice 0302 clinical medicine Calcium imaging Apolipoproteins E Alzheimer Disease Loss of Function Mutation medicine PSEN1 Presenilin-1 Animals Humans Regeneration Senile plaques Research Articles Visual Cortex Neurons Amyloid beta-Peptides Ecology business.industry Amyloidosis Neurodegeneration medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology nervous system Synapses Evoked Potentials Visual lipids (amino acids peptides and proteins) business Neuroscience Neuroglia 030217 neurology & neurosurgery Research Article |
| Zdroj: | Life Science Alliance Hudry, E, Klickstein, J, Cannavo, C, Jackson, R, Muzikansky, A, Gandhi, S, Urick, D, Sargent, T, Wrobleski, L, Roe, A D, Hou, S S, Kuchibhotla, K V, Betensky, R A, Spires-Jones, T & Hyman, B T 2019, ' Opposing Roles of apolipoprotein E in aging and neurodegeneration ', Life Science Alliance, vol. 2, no. 1 . https://doi.org/10.26508/lsa.201900325 |
| ISSN: | 2575-1077 |
| Popis: | This study investigates how APOE modulates neuronal function integrity during normal aging and in the context of amyloidosis. This work demonstrates that APOE is a necessary partner of Aβ-dependent neuronal dysfunction and synaptotoxicity but also preserves neuronal network during aging. Apolipoprotein E (APOE) effects on brain function remain controversial. Removal of APOE not only impairs cognitive functions but also reduces neuritic amyloid plaques in mouse models of Alzheimer’s disease (AD). Can APOE simultaneously protect and impair neural circuits? Here, we dissociated the role of APOE in AD versus aging to determine its effects on neuronal function and synaptic integrity. Using two-photon calcium imaging in awake mice to record visually evoked responses, we found that genetic removal of APOE improved neuronal responses in adult APP/PSEN1 mice (8–10 mo). These animals also exhibited fewer neuritic plaques with less surrounding synapse loss, fewer neuritic dystrophies, and reactive glia. Surprisingly, the lack of APOE in aged mice (18–20 mo), even in the absence of amyloid, disrupted visually evoked responses. These results suggest a dissociation in APOE’s role in AD versus aging: APOE may be neurotoxic during early stages of amyloid deposition, although being neuroprotective in latter stages of aging. |
| Databáze: | OpenAIRE |
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