Aβ dimers induce behavioral and neurochemical deficits of relevance to early Alzheimer's disease.
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.
['Abdel-Hafiz|Laila|L|', 'Müller-Schiffmann|Andreas|A|', 'Korth|Carsten|C|', 'Fazari|Benedetta|B|', 'Chao|Owen Y|OY|', 'Nikolaus|Susanne|S|', 'Schäble|Sandra|S|', 'Herring|Arne|A|', 'Keyvani|Kathy|K|', 'Lamounier-Zepter|Valéria|V|', 'Huston|Joseph P|JP|', 'de Souza Silva|Maria A|MA|']
D015102:3,4-Dihydroxyphenylacetic Acid D000109:Acetylcholine D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D000818:Animals D001522:Behavior, Animal D001921:Brain D001923:Brain Chemistry D004195:Disease Models, Animal D004298:Dopamine D006897:Hydroxyindoleacetic Acid D008297:Male D008822:Mice, Transgenic D012701:Serotonin D013315:Stress, Psychological
Alzheimer's disease tgDimer mouse Memory Acetylcholine 5-HT Amyloid β dimer