التفاصيل البيبلوغرافية
| العنوان: |
ABCA7-dependent Neuropeptide-Y signalling is a resilience mechanism required for synaptic integrity in Alzheimer's disease. |
| المؤلفون: |
Tayran H, Yilmaz E, Bhattarai P, Min Y, Wang X, Ma Y, Nelson N, Kassara N, Cosacak MI, Dogru RM, Reyes-Dumeyer D, Reddy JS, Qiao M, Flaherty D, Teich AF, Gunasekaran TI, Yang Z, Tosto G, Vardarajan BN, İş Ö, Ertekin-Taner N, Mayeux R, Kizil C |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jan 02. Date of Electronic Publication: 2024 Jan 02. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Alzheimer's disease (AD) remains a complex challenge characterized by cognitive decline and memory loss. Genetic variations have emerged as crucial players in the etiology of AD, enabling hope for a better understanding of the disease mechanisms; yet the specific mechanism of action for those genetic variants remain uncertain. Animal models with reminiscent disease pathology could uncover previously uncharacterized roles of these genes. Using CRISPR/Cas9 gene editing, we generated a knockout model for abca7, orthologous to human ABCA7 - an established AD-risk gene. The abca7 +/- zebrafish showed reduced astroglial proliferation, synaptic density, and microglial abundance in response to amyloid beta 42 (Aβ42). Single-cell transcriptomics revealed abca7 -dependent neuronal and glial cellular crosstalk through neuropeptide Y (NPY) signaling. The abca7 knockout reduced the expression of npy, bdnf and ngfra , which are required for synaptic integrity and astroglial proliferation. With clinical data in humans, we showed reduced NPY in AD correlates with elevated Braak stage, predicted regulatory interaction between NPY and BDNF , identified genetic variants in NPY associated with AD, found segregation of variants in ABCA7, BDNF and NGFR in AD families, and discovered epigenetic changes in the promoter regions of NPY, NGFR and BDNF in humans with specific single nucleotide polymorphisms in ABCA7 . These results suggest that ABCA7-dependent NPY signaling is required for synaptic integrity, the impairment of which generates a risk factor for AD through compromised brain resilience. |
| تواريخ الأحداث: |
Date Created: 20240123 Latest Revision: 20240123 |
| رمز التحديث: |
20240123 |
| مُعرف محوري في PubMed: |
PMC10802315 |
| DOI: |
10.1101/2024.01.02.573893 |
| PMID: |
38260408 |
| قاعدة البيانات: |
MEDLINE |
