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Morgantown, WV, United States

The present invention provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to stimulate the synthesis of proteins sufficient to consolidate long-term memory. The present invention also provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to downregulate PKC.


The present disclosure relates to a peripheral diagnostic method for screening Alzheimers disease in patients based on quantitatively measured complexity of skin-sampled fibroblast networks.


Patent
Blanchette Rockefeller Neurosciences Institute | Date: 2013-03-27

The present invention relates to compositions and methods to modulate -secretase and/or to improve cognitive ability. The invention further relates the improved/enhanced cognitive ability in diseased individuals, particularly Alzheimers 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).


Patent
Blanchette Rockefeller Neurosciences Institute | Date: 2014-02-10

Methods of diagnosing Alzheimers disease are provided. At least five methods of diagnostic measurements are presented: Method 1: Integrated score; Method 2: Average aggregate area per number of aggregates; Method 3: Cell migration analysis; Method 4: Fractal analysis; Method 5: Lacunarity Analysis. In certain embodiments, a sample of a subjects skin provides a network of fibroblasts that is imaged and a fractal dimension of the image is calculated. The fractal dimension can be compared to an aged-matched control (non-Alzheimers) database to determine if the subject has Alzheimers disease. The network of fibroblasts may be cultured in a matrix, for example in a protein mixture.


The present invention relates to methods of diagnosing Alzheimers Disease as well as to methods of confirming the presence or absence of Alzheimers Disease in a subject. The present invention is also directed to methods of identifying a lead compound useful for the treatment of Alzheimers Disease by contacting non-Alzheimers cells with an amyloid beta peptide, stimulating the cells with a protein kinase C activator, contacting the cells with a test compound, and determining the value of an Alzheimers Disease-specific molecular biomarker. The present invention is also directed to methods of diagnosing Alzheimers Disease in a subject by detecting alterations in the ratio of specific phosphorylated MAP kinase proteins in cells after stimulation with a protein kinase C activator. The Alzheimers Disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimers Disease, monitoring the progression of Alzheimers Disease in a subject and in screening methods for the identification of compounds for treating or preventing Alzheimers Disease. The invention is also directed to kits containing reagents for the detection and diagnosis of the presence or absence of Alzheimers Disease using the Alzheimers Disease-specific molecular biomarkers disclosed herein.

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