Loss of cholinergic neurons in the Nucleus Basalis of Meynert in Alzheimer's disease (AD) patients was one of the first discoveries of neuron loss in AD. Despite an intense focus on the cholinergic system in AD, the reason for this cholinergic neuron loss is yet unknown. In the present study we examined Abeta-induced pathology and neuron loss in the cholinergic system of the bigenic APP/PS1KI mouse model. Expression of the APP transgene was found in ChAT-positive neurons of motor nuclei accompanied by robust intracellular Abeta accumulation, whereas no APP expressing neurons and thus no intracellular Abeta accumulation were found in neither the forebrain or pons complexes, nor in the caudate putamen. This expression pattern was used as a model system to study the effect of intra- and extracellular Abeta accumulation on neuron loss in the cholinergic system. Stereological quantification revealed a loss of ChAT-positive neurons in APP/PS1KI mice only in the motor nuclei Mo5 and 7N accumulating intracellular Abeta. This study supports the hypothesis of intracellular Abeta accumulation as an early pathological alteration contributing to cell death in AD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neurobiolaging.2008.07.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Cortical reorganization following dorsal spinal injuries in newborn monkeys reveals a critical period in the development of the somatosensory cortex.
Proc Natl Acad Sci U S A
January 2025
Department of Psychology, Vanderbilt University, Nashville, TN 37240.
Lesions of the dorsal columns of the spinal cord in adult macaque monkeys lead to the loss of hand inputs and large-scale expansion of the face inputs in the hand region of the somatosensory cortex. Inputs from alternate spinal pathways do not reactivate the deafferented regions of area 3b. Here, we determined how transections of the dorsal columns done within a few days after birth affect the developing somatosensory cortex.
View Article and Find Full Text PDFThe role of CXCL12/CXCR4/CXCR7 axis in cognitive impairment associated with neurodegenerative diseases.
Brain Behav Immun Health
February 2025
Pediatric and Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children Medical Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Neurodegenerative diseases, including Alzheimer's Disease (AD), Parkinson's Disease (PD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS), are characterized by progressive neuronal loss and cognitive impairment (CI). The: Cysteine-X-cysteine chemokine ligand 12(CXCL12)/CXC chemokine receptor type 4 (CXCR4)/CXC chemokine receptor type 7 (CXCR7) axis has emerged as a critical molecular pathway in the development of CI in these disorders. This review explores the role of this axis in the pathogenesis of CI across these neurodegenerative diseases, synthesizing current evidence and its implications for targeted therapies.
View Article and Find Full Text PDFMicroglial double stranded DNA accumulation induced by DNase II deficiency drives neuroinflammation and neurodegeneration.
J Neuroinflammation
January 2025
State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing, 100190, China.
Background: Deoxyribonuclease 2 (DNase II) is pivotal in the clearance of cytoplasmic double stranded DNA (dsDNA). Its deficiency incurs DNA accumulation in cytoplasm, which is a hallmark of multiple neurodegenerative diseases. Our previous study showed that neuronal DNase II deficiency drove tau hyperphosphorylation and neurodegeneration (Li et al.
View Article and Find Full Text PDFAging and MPTP Sensitivity Depend on Molecular and Ultrastructural Signatures of Astroglia and Microglia in Mice Substantia Nigra.
Cell Mol Neurobiol
January 2025
Department of Neurophysiology, National Institute of Mental Health and Neurosciences, Hosur Road, Bengaluru, 560029, India.
Both astroglia and microglia show region-specific distribution in CNS and often maladapt to age-associated alterations within their niche. Studies on autopsied substantia nigra (SN) of Parkinson's disease (PD) patients and experimental models propose gliosis as a trigger for neuronal loss. Epidemiological studies propose an ethnic bias in PD prevalence, since Caucasians are more susceptible than non-whites.
View Article and Find Full Text PDFGenetic features and pharmacological rescue of novel Kv7.2 variants in patients with epilepsy.
J Med Genet
January 2025
Heilongjiang Provincial Key Laboratory of Child Development and Genetic Research, Harbin Medical University, Harbin, Heilongjiang, China
Background: Increasing evidence indicates a robust correlation between epilepsy and variants of the Kv7.2 () channel, which is critically involved in directing M-currents and regulating neuronal excitability within the nervous system. With the advancement of next-generation sequencing, the identification of variants has surged.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!