The molecular pathway linking a genetic variant to the common, non-familial form of Alzheimer's disease is revealed in Nature this week. The study boosts our knowledge of the pathology of this neurodegenerative disease, and hints at new directions for therapy.
People who carry a particular gene allele APOE4 can be over 10 times more likely to develop late-onset Alzheimer's disease (LOAD). Asa Abeliovich and colleagues now show that the pattern of gene expression in the brains of APOE4 carriers has similarities to the patterns of gene expression in LOAD patients, and suggest that this altered profile might be an early hallmark of the disease. They identify a handful of genes thought to regulate this unusual transcription profile, including novel and previously known regulators of the amyloid precursor protein (APP), a molecule that has long been implicated in Alzheimer's disease. Genetic variants found at two of the genes may even affect the age when LOAD may set in.
Finally, the team tested a possible therapy, the drug levetiracetam, which inhibits one of the genes identified, and is currently used clinically to treat seizures. The drug suppresses APP processing in cells cultured from APOE4 carriers, making it a molecule worthy of further study.