BACE inhibition-dependent repair of Alzheimer’s pathophysiology Article Swipe

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Neuroscience Mechanism (biology) Amyloid precursor protein secretase Amyloid (mycology) Alzheimer's disease Pathophysiology Amyloid precursor protein Amyloid β Disease Memory impairment Medicine Biology Pathology Cognition Philosophy Epistemology

Aylin D. Keskin , Maja Kekuš , Helmuth Adelsberger , Ulf Neumann , Derya R. Shimshek , Beomjong Song , Benedikt Zott , Tingying Peng , Hans Förstl , Matthias Staufenbiel , Israel Nelken , Bert Sakmann , Arthur Konnerth , Marc Aurel Busche ·

YOU? · · 2017 · Open Access · · DOI: https://doi.org/10.1073/pnas.1708106114 · OA: W2738200982

Significance The accumulation of amyloid-β (Aβ) proteins in the brain contributes to Alzheimer´s disease (AD). Reducing Aβ by inhibiting its production with a β-secretase (BACE) inhibitor represents a novel mechanism for treating AD; however, whether this therapeutic strategy is capable of repairing impaired brain circuits associated with AD is unknown. Here we demonstrate that BACE inhibition is beneficial to all levels of impairment in an AD mouse model: cellular, long-range circuitry, and memory. We provide evidence that the rescue is dependent on the reduction of soluble forms of Aβ surrounding amyloid plaques. These results have mechanistic and therapeutic implications for AD, including Aβ-related memory defects.