Matches in SemOpenAlex for { <https://semopenalex.org/work/W3175323930> ?p ?o ?g. }
- W3175323930 abstract "Abstract The human hippocampal formation plays a central role in Alzheimer’s disease (AD) progression, cognitive traits, and the onset of dementia; yet its molecular states in AD remain uncharacterized. Here, we report a comprehensive single-cell transcriptomic dissection of the human hippocampus and entorhinal cortex across 489,558 cells from 65 individuals with varying stages of AD pathology. We transcriptionally characterize major brain cell types and neuronal classes, including 17 glutamatergic and 8 GABAergic neuron subpopulations. Combining evidence from human and mouse tissue-microdissection, neuronal cell isolation and spatial transcriptomics, we show that single-cell expression patterns capture fine-resolution neuronal anatomical topography. By stratifying subjects into early and late pathology groups, we uncover stage-dependent and cell-type specific transcriptional modules altered during AD progression. These include early-stage cell-type specific dysregulation of cellular and cholesterol metabolism, late-stage neuron-glia alterations in neurotransmission, and late-stage signatures of cellular stress, apoptosis, and DNA damage broadly shared across cell types. Late-stage signatures show signs of convergence in hippocampal and cortical cells, while early changes diverge; highlighting the relevance of characterizing molecular pathology across brain regions and AD progression. Finally, we characterize neuron subregion-specific responses to AD pathology and show that CA1 pyramidal neurons are the most transcriptionally altered while CA3 and dentate gyrus granule neurons the least. Our study provides a valuable resource to extend cell type-specific studies of AD to clinically relevant brain regions affected early by pathology in disease progression." @default.
- W3175323930 created "2021-07-05" @default.
- W3175323930 creator A5000254294 @default.
- W3175323930 creator A5008820889 @default.
- W3175323930 creator A5026015872 @default.
- W3175323930 creator A5042440695 @default.
- W3175323930 creator A5042845284 @default.
- W3175323930 creator A5046586758 @default.
- W3175323930 creator A5068597405 @default.
- W3175323930 creator A5089947611 @default.
- W3175323930 creator A5089977648 @default.
- W3175323930 date "2021-07-01" @default.
- W3175323930 modified "2023-10-18" @default.
- W3175323930 title "Single-cell anatomical analysis of human hippocampus and entorhinal cortex uncovers early-stage molecular pathology in Alzheimer’s disease" @default.
- W3175323930 cites W1979283544 @default.
- W3175323930 cites W2005483591 @default.
- W3175323930 cites W2017666196 @default.
- W3175323930 cites W2055655674 @default.
- W3175323930 cites W2111212838 @default.
- W3175323930 cites W2125805216 @default.
- W3175323930 cites W2135771073 @default.
- W3175323930 cites W2265799967 @default.
- W3175323930 cites W2343439038 @default.
- W3175323930 cites W2345356016 @default.
- W3175323930 cites W2462053388 @default.
- W3175323930 cites W2581824660 @default.
- W3175323930 cites W2747841296 @default.
- W3175323930 cites W2761726094 @default.
- W3175323930 cites W2774835162 @default.
- W3175323930 cites W2800392236 @default.
- W3175323930 cites W2809330972 @default.
- W3175323930 cites W2885927965 @default.
- W3175323930 cites W2890004445 @default.
- W3175323930 cites W2891700860 @default.
- W3175323930 cites W2893655504 @default.
- W3175323930 cites W2896025743 @default.
- W3175323930 cites W2904175868 @default.
- W3175323930 cites W2904237875 @default.
- W3175323930 cites W2908002252 @default.
- W3175323930 cites W2908632279 @default.
- W3175323930 cites W2911725378 @default.
- W3175323930 cites W2931036699 @default.
- W3175323930 cites W2942678593 @default.
- W3175323930 cites W2946016273 @default.
- W3175323930 cites W2950976066 @default.
- W3175323930 cites W2951560273 @default.
- W3175323930 cites W2976163884 @default.
- W3175323930 cites W2983166786 @default.
- W3175323930 cites W2984472267 @default.
- W3175323930 cites W2991414673 @default.
- W3175323930 cites W2997504734 @default.
- W3175323930 cites W3013901493 @default.
- W3175323930 cites W3018541302 @default.
- W3175323930 cites W3022539327 @default.
- W3175323930 cites W3034077561 @default.
- W3175323930 cites W3037329734 @default.
- W3175323930 cites W3037608718 @default.
- W3175323930 cites W3042896257 @default.
- W3175323930 cites W3043048574 @default.
- W3175323930 cites W3089010583 @default.
- W3175323930 cites W3094007434 @default.
- W3175323930 cites W3103933599 @default.
- W3175323930 cites W3106188259 @default.
- W3175323930 cites W3157602736 @default.
- W3175323930 cites W3162218953 @default.
- W3175323930 cites W4247665917 @default.
- W3175323930 cites W610927360 @default.
- W3175323930 doi "https://doi.org/10.1101/2021.07.01.450715" @default.
- W3175323930 hasPublicationYear "2021" @default.
- W3175323930 type Work @default.
- W3175323930 sameAs 3175323930 @default.
- W3175323930 citedByCount "7" @default.
- W3175323930 countsByYear W31753239302022 @default.
- W3175323930 countsByYear W31753239302023 @default.
- W3175323930 crossrefType "posted-content" @default.
- W3175323930 hasAuthorship W3175323930A5000254294 @default.
- W3175323930 hasAuthorship W3175323930A5008820889 @default.
- W3175323930 hasAuthorship W3175323930A5026015872 @default.
- W3175323930 hasAuthorship W3175323930A5042440695 @default.
- W3175323930 hasAuthorship W3175323930A5042845284 @default.
- W3175323930 hasAuthorship W3175323930A5046586758 @default.
- W3175323930 hasAuthorship W3175323930A5068597405 @default.
- W3175323930 hasAuthorship W3175323930A5089947611 @default.
- W3175323930 hasAuthorship W3175323930A5089977648 @default.
- W3175323930 hasBestOaLocation W31753239301 @default.
- W3175323930 hasConcept C142724271 @default.
- W3175323930 hasConcept C148762608 @default.
- W3175323930 hasConcept C1491633281 @default.
- W3175323930 hasConcept C169760540 @default.
- W3175323930 hasConcept C170493617 @default.
- W3175323930 hasConcept C189014844 @default.
- W3175323930 hasConcept C2776464000 @default.
- W3175323930 hasConcept C2776925932 @default.
- W3175323930 hasConcept C2777670902 @default.
- W3175323930 hasConcept C2779134260 @default.
- W3175323930 hasConcept C2780648746 @default.
- W3175323930 hasConcept C2780715579 @default.
- W3175323930 hasConcept C2781161787 @default.
- W3175323930 hasConcept C502032728 @default.
- W3175323930 hasConcept C54355233 @default.