ArticleMolecular neurobiology2021
Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer's Disease.
Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 31 citations in OpenAlex.
- Preparation of Postmortem Human Formalin-Fixed Paraffin-Embedded Frontal Cortex Tissue for Profiling Pyramidal Neurons Via Digital Spatial Profiling.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Maternal Choline Supplementation in a Mouse Model of Down Syndrome and Alzheimer's Disease Generates Unique Expression Profile Mosaics Within Three Hippocampal Excitatory Neuronal Populations.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Neuronal gene profiling of tau oligomer-bearing cholinergic nucleus basalis neurons during the onset of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Aging, Rather than Genotype, Is the Principal Contributor to Differential Gene Expression Within Targeted Replacement APOE2, APOE3, and APOE4 Mouse Brain.Brain sciences · 2025Article
- Profiling lamina specific pyramidal neurons using postmortem human formalin fixed paraffin embedded frontal cortex tissue in combination with digital spatial profiling.Journal of neuroscience methods · 2025Article
- Benefits of Maternal Choline Supplementation on Aged Basal Forebrain Cholinergic Neurons (BFCNs) in a Mouse Model of Down Syndrome and Alzheimer's Disease.Biomolecules · 2025Article
- Frontal cortex pyramidal neuron expression profiles differentiate the prodromal stage from progressive degeneration across the Alzheimer's disease spectrum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Single-nucleus analysis reveals oxidative stress in Down syndrome basal forebrain neurons at birth.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Single-nucleus analysis reveals oxidative stress in Down syndrome basal forebrain neurons at birth.bioRxiv : the preprint server for biology · 2025Article
- Profiling hippocampal neuronal populations reveals unique gene expression mosaics reflective of connectivity-based degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.Frontiers in molecular neuroscience · 2025Article
- Maternal choline supplementation rescues early endosome pathology in basal forebrain cholinergic neurons in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.Neurobiology of aging · 2024Article
- Down syndrome frontal cortex layer III and layer V pyramidal neurons exhibit lamina specific degeneration in aged individuals.Acta neuropathologica communications · 2024Article
- Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome.The Journal of infectious diseases · 2024Review
- Analysis of microisolated frontal cortex excitatory layer III and V pyramidal neurons reveals a neurodegenerative phenotype in individuals with Down syndrome.Acta neuropathologica · 2024Article
- The ISR downstream target ATF4 represses long-term memory in a cell type-specific manner.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Streamlined Full-Length Total RNA Sequencing of Paraformaldehyde-Fixed Brain Tissues.International journal of molecular sciences · 2024Article
- Single-Cell Sequencing Technology and Its Application in the Study of Central Nervous System Diseases.Cell biochemistry and biophysics · 2024Review
- Hippocampal CA1 Pyramidal Neurons Display Sublayer and Circuitry Dependent Degenerative Expression Profiles in Aged Female Down Syndrome Mice.Journal of Alzheimer's disease : JAD · 2024Article
- Maternal choline supplementation protects against age-associated cholinergic and GABAergic basal forebrain neuron degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.Neurobiology of disease · 2023Article
- New perspectives on the basal forebrain cholinergic system in Alzheimer's disease.Neuroscience and biobehavioral reviews · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer's disease (AD). Current therapeutics have been unsuccessful in slowing disease progression, likely due to complex pathological interactions and dysregulated pathways that are poorly understood. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration. We utilized Ts65Dn mice to understand mechanisms underlying BFCN degeneration to identify novel targets for therapeutic intervention. We performed high-throughput, single population RNA sequencing (RNA-seq) to interrogate transcriptomic changes within medial septal nucleus (MSN) BFCNs, using laser capture microdissection to individually isolate ~500 choline acetyltransferase-immunopositive neurons in Ts65Dn and normal disomic (2N) mice at 6 months of age (MO). Ts65Dn mice had unique MSN BFCN transcriptomic profiles at ~6 MO clearly differentiating them from 2N mice. Leveraging Ingenuity Pathway Analysis and KEGG analysis, we linked differentially expressed gene (DEG) changes within MSN BFCNs to several canonical pathways and aberrant physiological functions. The dysregulated transcriptomic profile of trisomic BFCNs provides key information underscoring selective vulnerability within the septohippocampal circuit. We propose both expected and novel therapeutic targets for DS and AD, including specific DEGs within cholinergic, glutamatergic, GABAergic, and neurotrophin pathways, as well as select targets for repairing oxidative phosphorylation status in neurons. We demonstrate and validate this interrogative quantitative bioinformatic analysis of a key dysregulated neuronal population linking single population transcript changes to an established pathological hallmark associated with cognitive decline for therapeutic development in human DS and AD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.