@misc{oai:kawasakigakuen.repo.nii.ac.jp:00000304,
 author = {Shinji TAGAMI and Masatoshi TAKEDA and Masayasu OKOCHI},
 month = {Dec},
 note = {Alzheimer disease (AD) is the most common type of dementia and may account for 60 - 70% of dementia cases. Senile plaques are a hallmark of AD, and their major constituent is amyloid β-protein (Aβ) 42. Aβ is produced via endoproteolysis by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), which cleaves β-amyloid precursor protein at the extracellular domain, followed by cleavages by presenilin/γ-secretase. Aβ accumulation in the brain is thought to occur decades before disease onset, and pathological changes such as synaptic dysfunction and tau accumulation gradually proceed. Most candidates for disease-modifying therapy (DMT) for AD have targeted either inhibition of Aβ generation with secretase inhibitors or removal of produced and aggregated Aβ with anti-Aβ antibodies. None of them has been approved for clinical practice. Moreover, application of BACE inhibitors and γ-secretase inhibitors in several clinical studies caused paradoxical cognitive impairment. However, early AD patients treated with aducanumab, a monoclonal anti-Aβ antibody, showed a significant reduction in cognitive decline and its clinical use is awaiting approval by the FDA in 2020. In this review, we present a brief summary of DMTs that target Aβ and perspectives for future AD therapy., Review Article},
 title = {Clinical trials for Alzheimer disease and perspectives},
 year = {2020}
}