Methods for Alzheimer's disease treatment and cognitive enhancement
The present invention relates to compositions and methods to modulate α-secretase and/or to improve cognitive ability. The invention further relates the improved/enhanced cognitive ability in diseased individuals, particularly Alzheimer's Disease patients, and treatment thereof through increased sAPP production. Macrocyclic lactones (i.e. bryostatin class and neristatin class) are compounds preferred for use with the present composition. The present invention also provides methods for increasing the generation of non-amyloidogenic soluble APP comprising the activation of protein kinase C (PKC) by administering an effective amount of PKC activator(s).
1. A method for treating Alzheimer's disease, comprising administering a macrocyclic lactone chosen from bryostatin-2, bryostatin-3, bryostatin-4, bryostatin-5, bryostatin-6, bryostatin-7, bryostatin-8, bryostatin-9, bryostatin-10, bryostatin-11, bryostatin-12, bryostatin-13, bryostatin-14, bryostatin-15, bryostatin-16, bryostatin-17, and bryostatin 18 in a pharmaceutically acceptable carrier to a human patient in an amount effective to treat Alzheimer's Disease.
2. A method for enhancing cognitive ability in a human or animal subject with the Lewy-body variant of Alzheimer's disease with or without association with Parkinson's disease, comprising administering to the human or animal subject a macrocyclic lactone chosen from bryostatin-2, bryostatin-3, bryostatin-4, bryostatin-5, bryostatin-6, bryostatin-7, bryostatin-8, bryostatin-9, bryostatin-10, bryostatin-11, bryostatin-12, bryostatin-13, bryostatin-14, bryostatin-15, bryostatin-16, bryostatin-17, and bryostatin 18 in a pharmaceutically acceptable carrier in an amount effective to treat cognitive impairment in the human or animal subject with the Lewy-body variant of Alzheimer's disease with or without association with Parkinson's disease.