Decreased level of brain acetylcholine and memory disturbance in APPsw mice

• Published in: Neurobiology of aging Vol. 25; no. 4; pp. 483 - 490
• Main Authors: Ikarashi, Yasushi, Harigaya, Yasuo, Tomidokoro, Yasushi, Kanai, Mitsuyasu, Ikeda, Masaki, Matsubara, Etsuro, Kawarabayashi, Takeshi, Kuribara, Hisashi, Younkin, Steven G, Maruyama, Yuji, Shoji, Mikio
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01-04-2004; Elsevier Science
• Subjects: Acetylcholine; Acetylcholine - metabolism; Age Factors; Alzheimer’s disease; Amyloid beta-Protein Precursor - biosynthesis; Amyloid beta-Protein Precursor - genetics; Animals; APPsw mice; Biological and medical sciences; Brain - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Long-term memory; Medical sciences; Memory Disorders - genetics; Memory Disorders - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurology; Passive-avoidance task; Reaction Time - physiology; APPsw mice; Aβ; Long-term memory; Acetylcholine; Alzheimer’s disease; Passive-avoidance task; Nervous system diseases; Senescence; Alzheimer disease; Memory; Rodentia; Central nervous system; Long term; Cerebral disorder; Encephalon; Vertebrata; Mammalia; Mouse; β Amyloid protein; Animal; Central nervous system disease; Neurotransmitter; Degenerative disease; Alzheimer's disease
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/S0197-4580(03)00122-2

To clarify whether amyloid β protein (Aβ) amyloidosis induces a disturbance of cholinergic system leading to long-term memory deficits, we continuously examined memory disturbance using the passive-avoidance task, and measured Aβ burden and concentrations of acetylcholine in the brain of APPsw transgenic mice. Repetitive retention trials of the passive-avoidance task showed that the long-term memory impairment in APPsw mice appeared from ∼7.75 months old and progressively advanced. Significant decreases in acetylcholine levels were found in the brains of 10-month-old mice. A few senile plaques appeared in the cerebral cortex and the hippocampus at 8 months old, and increased in size and number with aging. The concentrations of brain Aβ40/42(43) gradually increased from 8 months old and exponentially increased thereafter. Advance of long-term memory disturbance was closely correlated with Aβ40/42(43) burden. These findings suggested that Aβ accumulation induced long-term memory impairment and disturbance of the cholinergic system, and that the passive-avoidance task and measuring acetylcholine were useful methods for evaluating this mouse model as well as Aβ accumulation.