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000272136 1001_ $$aTayran, Hüseyin$$b0
000272136 245__ $$aABCA7-dependent induction of neuropeptide Y is required for synaptic resilience in Alzheimer's disease through BDNF/NGFR signaling.
000272136 260__ $$aAmsterdam$$bElsevier$$c2024
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000272136 520__ $$aGenetic variants in ABCA7, an Alzheimer's disease (AD)-associated gene, elevate AD risk, yet its functional relevance to the etiology is unclear. We generated a CRISPR-Cas9-mediated abca7 knockout zebrafish to explore ABCA7's role in AD. Single-cell transcriptomics in heterozygous abca7+/- knockout combined with Aβ42 toxicity revealed that ABCA7 is crucial for neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), and nerve growth factor receptor (NGFR) expressions, which are crucial for synaptic integrity, astroglial proliferation, and microglial prevalence. Impaired NPY induction decreased BDNF and synaptic density, which are rescuable with ectopic NPY. In induced pluripotent stem cell-derived human neurons exposed to Aβ42, ABCA7-/- suppresses NPY. Clinical data showed reduced NPY in AD correlated with elevated Braak stages, genetic variants in NPY associated with AD, and epigenetic changes in NPY, NGFR, and BDNF promoters linked to ABCA7 variants. Therefore, ABCA7-dependent NPY signaling via BDNF-NGFR maintains synaptic integrity, implicating its impairment in increased AD risk through reduced brain resilience.
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000272136 650_7 $$2NLM Chemicals$$aBrain-Derived Neurotrophic Factor
000272136 650_7 $$2NLM Chemicals$$aNeuropeptide Y
000272136 650_7 $$2NLM Chemicals$$aATP-Binding Cassette Transporters
000272136 650_7 $$2NLM Chemicals$$aReceptors, Nerve Growth Factor
000272136 650_7 $$2NLM Chemicals$$aZebrafish Proteins
000272136 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000272136 650_2 $$2MeSH$$aBrain-Derived Neurotrophic Factor: metabolism
000272136 650_2 $$2MeSH$$aBrain-Derived Neurotrophic Factor: genetics
000272136 650_2 $$2MeSH$$aAnimals
000272136 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000272136 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000272136 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000272136 650_2 $$2MeSH$$aNeuropeptide Y: metabolism
000272136 650_2 $$2MeSH$$aNeuropeptide Y: genetics
000272136 650_2 $$2MeSH$$aHumans
000272136 650_2 $$2MeSH$$aZebrafish
000272136 650_2 $$2MeSH$$aSignal Transduction
000272136 650_2 $$2MeSH$$aSynapses: metabolism
000272136 650_2 $$2MeSH$$aSynapses: pathology
000272136 650_2 $$2MeSH$$aATP-Binding Cassette Transporters: genetics
000272136 650_2 $$2MeSH$$aATP-Binding Cassette Transporters: metabolism
000272136 650_2 $$2MeSH$$aReceptors, Nerve Growth Factor: genetics
000272136 650_2 $$2MeSH$$aReceptors, Nerve Growth Factor: metabolism
000272136 650_2 $$2MeSH$$aZebrafish Proteins: genetics
000272136 650_2 $$2MeSH$$aZebrafish Proteins: metabolism
000272136 650_2 $$2MeSH$$aNeurons: metabolism
000272136 650_2 $$2MeSH$$aNeurons: pathology
000272136 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000272136 650_2 $$2MeSH$$aAmyloid beta-Peptides: genetics
000272136 7001_ $$aYilmaz, Elanur$$b1
000272136 7001_ $$0P:(DE-2719)2811306$$aBhattarai, Prabesh$$b2$$udzne
000272136 7001_ $$aMin, Yuhao$$b3
000272136 7001_ $$aWang, Xue$$b4
000272136 7001_ $$aMa, Yiyi$$b5
000272136 7001_ $$aWang, Ni$$b6
000272136 7001_ $$aJeong, Inyoung$$b7
000272136 7001_ $$aNelson, Nastasia$$b8
000272136 7001_ $$aKassara, Nada$$b9
000272136 7001_ $$0P:(DE-2719)2811286$$aCosacak, Mehmet Ilyas$$b10$$udzne
000272136 7001_ $$aDogru, Ruya Merve$$b11
000272136 7001_ $$aReyes-Dumeyer, Dolly$$b12
000272136 7001_ $$aStenersen, Jakob Mørkved$$b13
000272136 7001_ $$aReddy, Joseph S$$b14
000272136 7001_ $$aQiao, Min$$b15
000272136 7001_ $$aFlaherty, Delaney$$b16
000272136 7001_ $$aGunasekaran, Tamil Iniyan$$b17
000272136 7001_ $$aYang, Zikun$$b18
000272136 7001_ $$aJurisch-Yaksi, Nathalie$$b19
000272136 7001_ $$aTeich, Andrew F$$b20
000272136 7001_ $$aKanekiyo, Takahisa$$b21
000272136 7001_ $$aTosto, Giuseppe$$b22
000272136 7001_ $$aVardarajan, Badri N$$b23
000272136 7001_ $$aİş, Özkan$$b24
000272136 7001_ $$aErtekin-Taner, Nilüfer$$b25
000272136 7001_ $$aMayeux, Richard$$b26
000272136 7001_ $$aKizil, Caghan$$b27
000272136 773__ $$0PERI:(DE-600)3110160-4$$a10.1016/j.xgen.2024.100642$$gVol. 4, no. 9, p. 100642 -$$n9$$p100642$$tCell genomics$$v4$$x2666-979X$$y2024
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