Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Disease Mouse Model
Several genetic studies have identified a rare variant of triggering receptor expressed on myeloid cells 2 (TREM2) as a risk factor for Alzheimer’s disease (AD). However, findings on the effects of TREM2 on Aβ deposition are quite inconsistent in animal studies, requiring further investigation. In t...
| Principais autores: | , , , , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
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MDPI AG
2021-05-01
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| coleção: | Molecules |
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| Acesso em linha: | https://www.mdpi.com/1420-3049/26/9/2685 |
| _version_ | 1827693416943714304 |
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| author | Qiuju Yuan Xiaodong Liu Yi Zhang Yan-Fang Xian Juntao Zou Xie Zhang Pengyun Huang You-Qiang Song Zhi-Xiu Lin |
| author_facet | Qiuju Yuan Xiaodong Liu Yi Zhang Yan-Fang Xian Juntao Zou Xie Zhang Pengyun Huang You-Qiang Song Zhi-Xiu Lin |
| author_sort | Qiuju Yuan |
| collection | DOAJ |
| description | Several genetic studies have identified a rare variant of triggering receptor expressed on myeloid cells 2 (TREM2) as a risk factor for Alzheimer’s disease (AD). However, findings on the effects of TREM2 on Aβ deposition are quite inconsistent in animal studies, requiring further investigation. In this study, we investigated whether elevation of TREM2 mitigates Aβ pathology in TgCRND8 mice. We found that peripheral nerve injury resulted in a robust elevation of TREM2 exclusively in reactive microglia in the ipsilateral spinal cord of aged TgCRND8 mice at the age of 20 months. TREM2 expression appeared on day 1 post-injury and the upregulation was maintained for at least 28 days. Compared to the contralateral side, neither amyloid beta plaque load nor soluble Aβ40 and Aβ42 levels were attenuated upon TREM2 induction. We further showed direct evidence that TREM2 elevation in reactive microglia did not affect amyloid-β pathology in plaque-bearing TgCRND8 mice by applying anti-TREM2 neutralizing antibody to selectively block TREM2. Our results question the ability of TREM2 to ameliorate established Aβ pathology, discouraging future development of disease-modifying pharmacological treatments targeting TREM2 in the late stage of AD. |
| first_indexed | 2024-03-10T11:43:21Z |
| format | Article |
| id | doaj.art-64ae3ae658fd4932be6a7f04a33572ce |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T11:43:21Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-64ae3ae658fd4932be6a7f04a33572ce2023-11-21T18:19:11ZengMDPI AGMolecules1420-30492021-05-01269268510.3390/molecules26092685Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Disease Mouse ModelQiuju Yuan0Xiaodong Liu1Yi Zhang2Yan-Fang Xian3Juntao Zou4Xie Zhang5Pengyun Huang6You-Qiang Song7Zhi-Xiu Lin8Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong KongDepartment of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong KongLi Ka Shing Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong KongFaculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong KongFaculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong KongFaculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong KongFaculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong KongLi Ka Shing Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong KongFaculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong KongSeveral genetic studies have identified a rare variant of triggering receptor expressed on myeloid cells 2 (TREM2) as a risk factor for Alzheimer’s disease (AD). However, findings on the effects of TREM2 on Aβ deposition are quite inconsistent in animal studies, requiring further investigation. In this study, we investigated whether elevation of TREM2 mitigates Aβ pathology in TgCRND8 mice. We found that peripheral nerve injury resulted in a robust elevation of TREM2 exclusively in reactive microglia in the ipsilateral spinal cord of aged TgCRND8 mice at the age of 20 months. TREM2 expression appeared on day 1 post-injury and the upregulation was maintained for at least 28 days. Compared to the contralateral side, neither amyloid beta plaque load nor soluble Aβ40 and Aβ42 levels were attenuated upon TREM2 induction. We further showed direct evidence that TREM2 elevation in reactive microglia did not affect amyloid-β pathology in plaque-bearing TgCRND8 mice by applying anti-TREM2 neutralizing antibody to selectively block TREM2. Our results question the ability of TREM2 to ameliorate established Aβ pathology, discouraging future development of disease-modifying pharmacological treatments targeting TREM2 in the late stage of AD.https://www.mdpi.com/1420-3049/26/9/2685Alzheimer’s diseaseTREM2microglia activationAβ depositionspinal cord |
| spellingShingle | Qiuju Yuan Xiaodong Liu Yi Zhang Yan-Fang Xian Juntao Zou Xie Zhang Pengyun Huang You-Qiang Song Zhi-Xiu Lin Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Disease Mouse Model Molecules Alzheimer’s disease TREM2 microglia activation Aβ deposition spinal cord |
| title | Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Disease Mouse Model |
| title_full | Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Disease Mouse Model |
| title_fullStr | Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Disease Mouse Model |
| title_full_unstemmed | Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Disease Mouse Model |
| title_short | Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer’s Disease Mouse Model |
| title_sort | established beta amyloid pathology is unaffected by trem2 elevation in reactive microglia in an alzheimer s disease mouse model |
| topic | Alzheimer’s disease TREM2 microglia activation Aβ deposition spinal cord |
| url | https://www.mdpi.com/1420-3049/26/9/2685 |
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