Affiliations: [a] Department of Neurology, Inovation Center for Neurological Disorders, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China | [b] Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China | [c] Clinical Center for Neurodegenerative Disease and Memory Impairment, Capital Medical University, Beijing, P.R. China | [d] Center of Alzheimer’s Disease, Beijing Institute for Brain Disorders, Beijing, P.R. China | [e] Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, P.R. China | [f] National Clinical Research Center for Geriatric Disorders, Beijing, P.R. China
Correspondence:
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Correspondence to: Jian-Ping Jia, Inovation Center for Neurological Disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, P.R. China. Tel.: +86 10 83199449; Fax: +86 1083171070; E-mail: [email protected].
Note: [1] These authors contribute equally to this work.
Abstract: Abnormal amyloid-β (Aβ) aggregates are a striking feature of Alzheimer’s disease (AD), and Aβ oligomers have been proven to be crucial in the pathology of AD. Any intervention targeting the generation or aggregation of Aβ can be expected to be useful in AD treatment. Oxidative stress and inflammation are common pathological changes in AD that are involved in the generation and aggregation of Aβ. In the present study, 6-month-old PS1V97L transgenic (Tg) mice were treated with sulforaphane, an antioxidant, for 4 months, and this treatment significantly inhibited the generation and aggregation of Aβ. Sulforaphane also alleviated several downstream pathological changes that including tau hyperphosphorylation, oxidative stress, and neuroinflammation. Most importantly, the cognition of the sulforaphane-treated PS1V97L Tg mice remained normal compared to that of wild-type mice at 10 months of age, when dementia typically emerges in PS1V97L Tg mice. Pretreating cultured cortical neurons with sulforaphane also protected against neuronal injury caused by Aβ oligomers in vitro. These findings suggest that sulforaphane may be a potential compound that can inhibit Aβ oligomer production in AD.
