In Alzheimer’s disease (AD) patients, rapamycin treatment could aggravate beta-amyloid related pathologies, a new mouse study indicates. Researchers show rapamycin taken orally inhibits the mTOR signaling pathway in microglial cells in the brain that regulates cell metabolism. This down-regulates a gene called Trem2. Trem2 is a receptor located on the surface of microglia that enables these cells to engulf and degrade β-amyloid. Loss of Trem2 in microglia impairs amyloid degradation, which in turn causes a buildup of β-amyloid plaques.
A new study suggests the depletion of soluble beta amyloid and not the increase of insoluble beta amyloid plaques may be the underlying cause of Alzheimer’s disease. Based on the evidence that despite the presence of brain amyloid plaques, individuals with normal cognition had higher soluble amyloid levels than individuals with mild cognitive impairment or Alzheimer’s disease, the team proposes increasing soluble beta amyloid as a treatment option.