Biomarkers, assays, and therapies for Alzheimer disease.

The initial pathophysiologic changes of AD are found in the hippocampus region of the brain, disrupting memory and the ability to learn. AD progression is linked to nerve cell dysfunction and cell death due to the accumulation of 2 protein aggregates: -amyloid (A ) and tau. In the cerebrospinal fluid (CSF), these proteins are biomarkers for AD. Cleavage of the amyloid precursor protein (APP) generates varying lengths of A peptides (38 – 43 amino acids) that accumulate in the extracellular space. Of these monomers, A -42 is the major form associated with AD. In addition, tau entanglement is also associated with AD and consists of insoluble hyperphosphorylated tau protein in the intracellular space. Both total tau (t-tau) and phosphorylated tau (p-tau) proteins are measured and associated with AD. Currently, clinical trials are testing therapies that target these proteins in hopes to delay or halt the cognitive decline in AD patients.