التفاصيل البيبلوغرافية
| العنوان: |
Neuronal APOE4-induced Early Hippocampal Network Hyperexcitability in Alzheimer's Disease Pathogenesis. |
| المؤلفون: |
Tabuena DR, Jang SS, Grone B, Yip O, Aery Jones EA, Blumenfeld J, Liang Z, Koutsodendris N, Rao A, Ding L, Zhang AR, Hao Y, Xu Q, Yoon SY, Leon S, Huang Y, Zilberter M |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 03. Date of Electronic Publication: 2024 Jul 03. |
| نوع المنشور: |
Journal Article; Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
The full impact of apolipoprotein E4 (APOE4), the strongest genetic risk factor for Alzheimer's disease (AD), on neuronal and network function remains unclear. We found hippocampal region-specific network hyperexcitability in young APOE4 knock-in (E4-KI) mice which predicted cognitive deficits at old age. Network hyperexcitability in young E4-KI mice was mediated by hippocampal region-specific subpopulations of smaller and hyperexcitable neurons that were eliminated by selective removal of neuronal APOE4. Aged E4-KI mice exhibited hyperexcitable granule cells, a progressive inhibitory deficit, and E/I imbalance in the dentate gyrus, exacerbating hippocampal hyperexcitability. Single-nucleus RNA-sequencing revealed neuronal cell type-specific and age-dependent transcriptomic changes, including Nell2 overexpression in E4-KI mice. Reducing Nell2 expression in specific neuronal types of E4-KI mice with CRISPRi rescued their abnormal excitability phenotypes, implicating Nell2 overexpression as a cause of APOE4-induced hyperexcitability. These findings highlight the early transcriptomic and electrophysiological alterations underlying APOE4-induced hippocampal network dysfunction and its contribution to AD pathogenesis with aging. |
| معلومات مُعتمدة: |
P01 AG073082 United States AG NIA NIH HHS; R01 AG061150 United States AG NIA NIH HHS; R01 AG071697 United States AG NIA NIH HHS |
| تواريخ الأحداث: |
Date Created: 20230911 Latest Revision: 20240709 |
| رمز التحديث: |
20240709 |
| مُعرف محوري في PubMed: |
PMC10491126 |
| DOI: |
10.1101/2023.08.28.555153 |
| PMID: |
37693533 |
| قاعدة البيانات: |
MEDLINE |
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