Acetylcholinesterase-Positive Fiber Deafferentation and Cell Shrinkage in the Septohippocampal Pathway of Aged Amyloid Precursor Protein London Mutant Transgenic Mice

doi:10.1006/nbdi.2000.0283

Neurobiology of Disease

Volume 7, Issue 3, June 2000, Pages 152-168

https://doi.org/10.1006/nbdi.2000.0283 Get rights and content

Abstract

Several lines of evidence implicate a cholinergic deficit in Alzheimer's disease (AD). Transgenic mice that overexpress clinical mutants of the human amyloid precursor protein (APP) have been generated that recapitulate many aspects of AD. We now analyzed the cholinergic system in aged APP/London transgenic mice. The major finding was the reorganization of acetylcholinesterase-positive fibers within the hippocampus and the reduced size of cholinergic cells in the medial septum. The reduction of acetylcholinesterase-positive fibers in the subiculum together with increased fiber density in the CA1 and in the dentate gyrus suggests a synaptic sprouting compensatory mechanism within the hippocampus. In the cortex, amyloid plaques were associated with intense acetylcholinesterase activity and surrounded by dystrophic acetylcholinesterase-positive fibers. Nevertheless, the overall pattern of cholinergic innervation was unchanged. These results demonstrate that overexpression of APP/London caused, besides amyloid plaques in aged mouse brain, also cholinergic deafferentation and cholinergic cell shrinkage.

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¹: Present address: Department of Functional Genomics, Janssen Research Foundation, Beerse, Belgium.

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Regular ArticleAcetylcholinesterase-Positive Fiber Deafferentation and Cell Shrinkage in the Septohippocampal Pathway of Aged Amyloid Precursor Protein London Mutant Transgenic Mice

Abstract

Neurochem. Int.

Anal. Biochem.

Exp. Cell. Res.

Neurosci. Lett.

Trends Neurosci.

Biochem. Pharmacol.

Subiculum. Brain. Res.

Exp. Neurol.

Trends Neurosci.

Cell

Mol. Brain Res.

Neuron

Behav. Brain Res.

J. Biol. Chem.

Trends Neurosci.

Neurodegeneration

Neuroscience

Anal. Biochem.

Neurobiol. Aging

Estimation of nuclear population from microtome sections

Anat. Rec.

Stable complexes involving acetylcholinesterase and amyloid-β-peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils

J. Neurosci.

Effects of aging on nicotinic and muscarinic autoreceptor function in the rat brain: Relationship to presynaptic cholinergic markers and binding sites

J. Neurosci.

Cortical load of PHF-tau in Alzheimer's disease is correlated with cholinergic dysfunction

J. Neural. Transm.

Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer's disease and Parkinson's disease

J. Neurochem.

Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition

Nat. Genet.

Characterization of new polyclonal antibodies specific for 40 and 42 amino acid-long amyloid beta peptides: Their use to examine the cell biology of presenilins and the immunohistochemistry of sporadic Alzheimer's disease and cerebral amyloid angiopathy cases

Mol. Med.

Neurochemical correlates of dementia severity in Alzheimer's diasesae relative importance of the cholinergic system

J. Neurochem.

High affinity choline transporter status in Alzheimer's disease tissue from rapid autopsy

Ann. N. Y. Acad. Sci.

Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease

J. Neurophatol. Exp. Neurol.

Neuron loss in APP transgenic mice

Nature

Disruption of a single allele of the nerve growth factor gene results in atrophy of basal forebrain cholinergic neurons and memory deficits

J. Neurosci.

The projection from hippocampal area CA1 to the subiculum sustains long-term potentiation

Neuroreport

Neuropsychiatric aspects of Alzheimer's disease: The cholinergic hypothesis revisited

Neurology

Cholinergic markers in elderly patients with early signs of Alzheimer's disease

JAMA

The septohippocanpal pathway: Structure and function of a central cholinergic system

Physiol. Rev.

Endogenous FGF-2 is important for cholinergic sprouting in the denevervated hippocampus

J. Neurosci.

A rapid radiochemical method for the determination of choline acetyl transferase

J. Neurochem.

Regular Article
Acetylcholinesterase-Positive Fiber Deafferentation and Cell Shrinkage in the Septohippocampal Pathway of Aged Amyloid Precursor Protein London Mutant Transgenic Mice