Aβ dimers induce behavioral and neurochemical deficits of relevance to early Alzheimer's disease
Journal
Neurobiology of Aging
Series/Report No.
Neurobiology of Aging
Journal Volume
69
Start Page
1-9
ISSN
0197-4580
Date Issued
2018-09
Author(s)
Abdel-Hafiz, Laila
Müller-Schiffmann, Andreas
Korth, Carsten
Fazari, Benedetta
Nikolaus, Susanne
Schäble, Sandra
Herring, Arne
Keyvani, Kathy
Lamounier-Zepter, Valéria
Huston, Joseph P.
de Souza Silva, Maria A.
Abstract
We examined behaviors and neurotransmitter levels in the tgDimer mouse, a model for early Alzheimer's disease, that expresses exclusively soluble amyloid beta (Aβ) dimers and is devoid of Aβ plaques, astrogliosis, and neuroinflammation. Seven-month-old mice were subjected to tests of motor activity, attention, anxiety, habituation learning, working memory, and depression-related behaviors. They were impaired in nonselective attention and motor learning and showed anxiety- and despair-related behaviors. In 7- and 12-month-old mice, levels of acetylcholine, dopamine, and serotonin were measured in neostriatum, ventral striatum, prefrontal cortex, hippocampus, amygdala, and entorhinal cortex by high-performance liquid chromatography. The tgDimer mice had lower serotonin turnover rates in hippocampus, ventral striatum, and amygdala relative to wild type controls. The aged tgDimer mice had less hippocampal acetylcholine than adult tgDimers. Stress-test results, based on corticosterone levels, indicated an intact hypothalamus-pituitary-adrenal axis in 12-month-old mice. Since neither Aβ plaques nor astrogliosis or neuroinflammation was responsible for these phenotypes, we conclude that Aβ dimers contribute to neurotransmitter dysfunction and behavioral impairments, characteristic for the early stages of Alzheimer's disease.
Subjects
5-HT
Acetylcholine
Alzheimer's disease
Amyloid β dimer
Memory
tgDimer mouse
Publisher
Elsevier BV
Type
journal article