The lateral entorhinal cortex is a hub for local and global dysfunction in early Alzheimer's disease states.

Autor:	Mandino F; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.; Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.; Department of Radiology and Bioimaging Sciences, Yale School of Medicine, New Haven, CT, USA., Yeow LY; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Bi R; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Sejin L; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Bae HG; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.; Department of Life Sciences, Yeungnam University, Gyeongsan, South Korea., Baek SH; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Lee CY; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Mohammad H; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Horien C; Department of Radiology and Bioimaging Sciences, Yale School of Medicine, New Haven, CT, USA., Teoh CL; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Lee JH; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Lai MK; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Jung S; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Fu Y; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Olivo M; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore., Gigg J; Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK., Grandjean J; Singapore Bioimaging Consortium, Agency for Science, Technology and Research, Singapore.; Department of Radiology and Nuclear Medicine & Donders Institute for Brain, Cognition, and Behaviour, Donders Institute, Radboud University Medical Centre, The Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism [J Cereb Blood Flow Metab] 2022 Sep; Vol. 42 (9), pp. 1616-1631. Date of Electronic Publication: 2022 Apr 25.
DOI:	10.1177/0271678X221082016
Abstrakt:	Functional network activity alterations are one of the earliest hallmarks of Alzheimer's disease (AD), detected prior to amyloidosis and tauopathy. Better understanding the neuronal underpinnings of such network alterations could offer mechanistic insight into AD progression. Here, we examined a mouse model (3xTgAD mice) recapitulating this early AD stage. We found resting functional connectivity loss within ventral networks, including the entorhinal cortex, aligning with the spatial distribution of tauopathy reported in humans. Unexpectedly, in contrast to decreased connectivity at rest, 3xTgAD mice show enhanced fMRI signal within several projection areas following optogenetic activation of the entorhinal cortex. We corroborate this finding by demonstrating neuronal facilitation within ventral networks and synaptic hyperexcitability in projection targets. 3xTgAD mice, thus, reveal a dichotomic hypo-connected:resting versus hyper-responsive:active phenotype. This strong homotopy between the areas affected supports the translatability of this pathophysiological model to tau-related, early-AD deficits in humans.
Databáze:	MEDLINE
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