Disclosed herein are compositions and methods for treating and preventing neurodegenerative diseases, such as Alzheimer's disease. In some embodiments, the composition comprises a peptide that disrupts the binding between PTPs and APP, preventing ß-amyloidogenic processing of APP without affecting other major substrates of ß- and ?-secretases. Alternatively, in some embodiments, an antibody or a fragment of an antibody against PTPs or APP may be used to disrupt the binding between PTPs and APP. In some embodiments, the composition comprises compounds or enzymes, which restore perineuronal balance of PTPs ligands CS and HS, thereby preventing abnormally increased ß-amyloidogenic processing of APP. Compositions and methods disclosed herein can be used in combination to treat and prevent neurodegenerative diseases.
