Geon Alzheimer's Disease: Prevention and Therapy Papers



It has been well established that aerobic exercise can increase the production of brain-derived neurotrophic factor (BDNF), thus beneficial for the prevention of Alzheimer's disease (AD). In ApoE4 carriers, this capacity could be impaired. They may consider other approaches to increase BDNF such as intellectual activity, melatonin and lithium. On the basis of the BDNF Cascade Hypothesis, therapeutic development should target the steps before Ca2+ overload in the cascade, since the dramatically increased cytosolic Ca2+ may trigger a variety of damaging processes that would be very hard to inhibit. Aβ-targeting therapies are not recommended because Aβ production, and subsequent formation of Aβ oligomers and plaques, occur after Ca2+ overload. The most promising target could be the 4-repeat Tau, which plays a pivotal role in hyperexcitability (Paper 2) and consequently Ca2+ overload. On the other hand, the antibody against Tau's phosphatase-activating domain (PAD) is likely to alleviate disease progression as PAD exposure is critical for pathology spreading (Paper 10).


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