Intracellular Aß triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease. 2010

Ditte Z Christensen, and Thomas A Bayer, and Oliver Wirths
Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University of Goettingen, von-Siebold-Str. 5, 37075 Goettingen, Germany.

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.

UI MeSH Term Description Entries
D007424 Intracellular Fluid The fluid inside CELLS. Fluid, Intracellular,Fluids, Intracellular,Intracellular Fluids
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009410 Nerve Degeneration Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways. Neuron Degeneration,Degeneration, Nerve,Degeneration, Neuron,Degenerations, Nerve,Degenerations, Neuron,Nerve Degenerations,Neuron Degenerations
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002799 Cholinergic Fibers Nerve fibers liberating acetylcholine at the synapse after an impulse. Cholinergic Fiber,Fiber, Cholinergic,Fibers, Cholinergic
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016229 Amyloid beta-Peptides Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. Alzheimer beta-Protein,Amyloid Protein A4,Amyloid beta-Peptide,Amyloid beta-Protein,beta Amyloid,beta-Amyloid Protein,Alzheimer's ABP,Alzheimer's Amyloid Fibril Protein,Amyloid AD-AP,Amyloid Fibril Protein, Alzheimer's,Amyloid beta-Proteins,ABP, Alzheimer's,AD-AP, Amyloid,Alzheimer ABP,Alzheimer beta Protein,Alzheimers ABP,Amyloid AD AP,Amyloid beta Peptide,Amyloid beta Peptides,Amyloid beta Protein,Amyloid beta Proteins,Amyloid, beta,Protein A4, Amyloid,Protein, beta-Amyloid,beta Amyloid Protein,beta-Peptide, Amyloid,beta-Peptides, Amyloid,beta-Protein, Alzheimer,beta-Protein, Amyloid,beta-Proteins, Amyloid

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