Novel genes involved in vascular dysfunction of the middle temporal gyrus in Alzheimer’s disease: transcriptomics combined with machine learning analysis DOI Creative Commons
Meiling Wang,

Aojie He,

Yubing Kang

и другие.

Neural Regeneration Research, Год журнала: 2024, Номер 20(12), С. 3620 - 3634

Опубликована: Июль 29, 2024

JOURNAL/nrgr/04.03/01300535-202512000-00030/figure1/v/2025-01-31T122243Z/r/image-tiff Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer’s disease. The middle temporal gyrus region brain susceptible pronounced impairment in Identification molecules involved aberrance would support elucidation mechanisms underlying disease and discovery novel targets for intervention. We carried out single-cell transcriptomic analysis brains patients with healthy controls, revealing obvious changes function. CellChat intercellular communication showed number cell interactions this was decreased patients, altered endothelial cells pericytes being most prominent. Differentially expressed genes were also identified. Using results, AUCell evaluation pathway activity specific function directly growth factor (VEGF)A–VEGF receptor (VEGFR) 2 pathway. identified subtypes VEGFA–VEGFR2 activity. Two significant alteration AD: high expression Erb-B2 tyrosine kinase 4 (ERBB4 ) angiopoietin-like (ANGPTL4 ). Finally, combining bulk RNA sequencing data two machine learning algorithms (least absolute shrinkage selection operator random forest), four characteristic feature identified: somatostatin ( SST ), protein phosphatase non-receptor type 3 PTPN3 glutinase GL3 tropomyosin PTM3 These downregulated may be used target VEGF mouse models demonstrated consistent these gyrus. In conclusion, study detected between functioning findings contribute a deeper understanding molecular present treatment targets.

Язык: Английский

Low-Density Lipoprotein Receptor-Related Protein 1 as a Potential Therapeutic Target in Alzheimer’s Disease DOI Creative Commons
Sabrina Petralla,

Maria Panayotova,

Elisa Franchina

и другие.

Pharmaceutics, Год журнала: 2024, Номер 16(7), С. 948 - 948

Опубликована: Июль 17, 2024

Alzheimer’s disease (AD) is a progressive neurodegenerative impacting the lives of millions people worldwide. The formation amyloid β (Aβ) plagues in brain main pathological hallmark AD. Aβ deposits are formed due to imbalance between production and clearance across blood–brain barrier (BBB). In this respect, low-density lipoprotein receptor-related protein 1 (LRP1) plays significant role by mediating both clearance. Due its important AD pathogenesis, LRP1 considered an attractive drug target for therapies. present review, we summarize current knowledge about pathogenesis as well recent findings on changes expression function Finally, discuss advances utilizing treatments future perspectives research.

Язык: Английский

Процитировано

6
Altered glia-neuron communication in Alzheimer’s Disease affects WNT, p53, and NFkB Signaling determined by snRNA-seq DOI Creative Commons
Tabea M. Soelter, Timothy C. Howton, Amanda D. Clark

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 7, 2024

Alzheimer's disease is the most common cause of dementia and characterized by amyloid-β plaques, tau neurofibrillary tangles, neuronal loss. Although loss a primary hallmark disease, it known that non-neuronal cell populations are ultimately responsible for maintaining brain homeostasis health through neuron-glia glial crosstalk. Many signaling pathways have been proposed to be dysregulated in including WNT, TGFβ, p53, mTOR, NFkB, Pi3k/Akt signaling. Here, we predict altered cell-cell communication between glia neurons.

Язык: Английский

Процитировано

5
Stereo-seq of the prefrontal cortex in aging and Alzheimer’s disease DOI Creative Commons

Yun Gong,

Mohammad Haeri, Xiao Zhang

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 8, 2025

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in prefrontal cortex (PFC). We present first subcellular-resolution spatial transcriptome atlas of human (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages age-matched controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions laminar structure, exposed AD-related shifts layer-to-layer cell-cell interactions. Notably, we identified genes highly upregulated stressed neurons nearby glial cells, where diminished stress-response interactions that promote Aβ clearance. Further, cell-type-specific co-expression analysis three neuronal modules linked to neuroprotection, protein dephosphorylation, regulation, all downregulated as progresses. ZNF460 a transcription factor regulating these modules, offering potential therapeutic target. In summary, this provides valuable insight into AD's molecular mechanisms. (AD). Here, authors AD, revealing alterations.

Язык: Английский

Процитировано

0
Hallmarks of aging and Alzheimer’s Disease pathogenesis: paving the route for new therapeutic targets DOI

Federico Bellelli,

Davide Angioni, Beatrice Arosio

и другие.

Ageing Research Reviews, Год журнала: 2025, Номер 106, С. 102699 - 102699

Опубликована: Фев. 20, 2025

Язык: Английский

Процитировано

0
Psychiatric Genomics 2025 DOI
Chunyu Liu, Chunling Zhang, Stephen J. Glatt

и другие.

Psychiatric Clinics of North America, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Evaluation of altered cell–cell communication between glia and neurons in the hippocampus of 3xTg‐AD mice at two time points DOI Creative Commons
Tabea M. Soelter, Timothy C. Howton, Elizabeth Wilk

и другие.

Journal of Cell Communication and Signaling, Год журнала: 2025, Номер 19(1)

Опубликована: Фев. 28, 2025

Язык: Английский

Процитировано

0
Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer’s disease: A narrative review DOI Creative Commons

Anna Maggiore,

Valentina Latina, Maria D’Erme

и другие.

Ageing Research Reviews, Год журнала: 2024, Номер 102, С. 102578 - 102578

Опубликована: Ноя. 13, 2024

Alzheimer's Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on healthcare system, society, and economy due to increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques tau protein neurofibrillary tangles, which are two main hallmarks this devastating neurodegenerative disease, have not provided results in terms their neuropathological outcomes nor met expected clinical end-points. Ageing, genetic environmental risk factors, along different symptoms suggest that AD complex heterogeneous disorder multiple interconnected pathological pathways rather than single entity. In present review, we highlight discuss various non-canonical, Aβ-independent mechanisms, like gliosis, unhealthy dietary intake, lipid sugar signaling, cerebrovascular damage contribute onset development AD. We emphasize challenging traditional "amyloid cascade hypothesis" may improve our understanding age-related syndrome help fight progressive cognitive decline

Язык: Английский

Процитировано

3
Spatial Dissection of the Distinct Cellular Responses to Normal Aging and Alzheimer′s Disease in Human Prefrontal Cortex at Single-Nucleus Resolution DOI Creative Commons

Yun Gong,

Mohammad Haeri, Xiao Zhang

и другие.

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 22, 2024

Aging significantly elevates the risk for Alzheimer's disease (AD), contributing to accumulation of AD pathologies, such as amyloid-β (Aβ), inflammation, and oxidative stress. The human prefrontal cortex (PFC) is highly vulnerable impacts both aging AD. Unveiling understanding molecular alterations in PFC associated with normal (NA) essential elucidating mechanisms progression developing novel therapeutics this devastating disease. In study, first time, we employed a cutting-edge spatial transcriptome platform, STOmics

Язык: Английский

Процитировано

1
Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer's disease DOI Creative Commons
Zhongming Zhao, Andi Liu, Citu Citu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

Sporadic early-onset Alzheimer's disease (sEOAD) represents a significant but less-studied subtype of (AD). Here, we generated single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal and hippocampus nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes linked candidate

Язык: Английский

Процитировано

1
Single-nucleus multi-omics identifies shared and distinct pathways in Pick's and Alzheimer's disease DOI Creative Commons
Zechuan Shi,

Sudeshna Das,

Samuel Morabito

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 8, 2024

The study of neurodegenerative diseases, particularly tauopathies like Pick's disease (PiD) and Alzheimer's (AD), offers insights into the underlying regulatory mechanisms. By investigating epigenomic variations in these conditions, we identified critical changes driving progression, revealing potential therapeutic targets. Our comparative analyses uncovered disease-enriched non-coding regions genome-wide transcription factor (TF) binding differences, linking them to target genes. Notably, a distal human-gained enhancer (HGE) associated with E3 ubiquitin ligase (UBE3A), highlighting disease-specific alterations. Additionally, fine-mapping AD risk genes loci enriched microglial enhancers accessible other cell types. Shared distinct TF patterns were observed neurons glial cells across PiD AD. We validated our findings using CRISPR excise predicted region UBE3A developed an interactive database (http://swaruplab.bio.uci.edu/scROAD) visualize single-cell occupancy networks.

Язык: Английский

Процитировано

1