Hello there, BSR readers; it’s good to be back. It’s been a while since I’ve posted anything—that’s because I’ve recently made some pretty big life transitions. After graduating from the Psychology Department last May, I was lucky enough to land a job at Stanford Research International. While I miss being able to protest between classes, and study in trees, and though I often find myself overwhelmed with Silicon Valley preppies, it has been a wonderful experience thus far. I am currently participating in wonderful and novel Alzheimer’s research in Joseph Rogers’s laboratory of the neurobiology of aging. I want to share with you the science that has motivated me.
Before we talk cures, I need to first explain the disease itself. Alzheimer’s disease (AD) is a neurodegenerative disorder that is the sixth-leading cause of death in the United Sates and affects an estimated 5.4 million Americans. AD most often occurs later in life. It is characterized by progressive deterioration of brain function, and ultimately leads to death. On a cellular level, AD is associated with loss of neurons and synaptic connections within the cerebral cortex. AD patients also experience atrophy of many brain regions including the amygdala (which is dedicated to management of basic emotions), the frontal lobe (the part of the brain responsible for logic and behavior regulation), and the hippocampus (which aids memory).
Regardless of the large body of research that has been dedicated to AD, and despite the well-understood neuropathology of this disease, the root cause of this disorder remains obscure. The most widely accepted hypothesis for the cause of AD is the amyloid hypothesis, which postulates that the primary cause stems from deposits of the peptide amyloid beta (Abeta) within the brain. Abeta is a multifunctional protein that facilitates many processes (including kinase activation and regulation of cholesterol transport). However, Abeta is highly elevated in AD patients, causing the protein to form aggregates (called plaques) within the brain. In large enough amounts, these plaques initiate the damage to neurons.
It was long thought that the brain did not need any form of an immune system, because the brain is shielded from neuroinflammation by the impenetrable blood-brain barrier (BBB). In the 1980s, Joseph Rogers disproved this argument by finding strong evidence for a role of immune defense by microglial cells (non-neuronal brain cells). Microglials act like macrophages of the central nervous system, engulfing plaques and other infectious agents. So, in AD, microglial cells are activated in response to the plaques of Abeta that are formed. It is now known that the brain and peripheral immune systems play a key role in the development and maintenance of AD. Since his work in the 80s, Joe has shown that microglial activation, and other components of the inflammatory response (more specifically, the compliment cascade), occur in almost all major age-related brain disorders.
Numerous studies have shown that nonsteroidal anti-inflammatory drugs may delay the onset of AD, or slow the progression of AD in already-diagnosed patients. In other words, suppression of the immune response appears to hinder the onset of AD. Now, this creates quite a paradox: if immune responses are involved in the clearance of Abeta out of the body, and if large amounts of Abeta are involved in AD, how is it possible that suppressing the immune response would suppress AD development? My boss has some innovative ideas of why this may be so, most of which I cannot tell you (yet). But I can tell you that the progress is awesome! Currently, we are focusing on other ways that Abeta could be interacting with the immune system, while also trying to pinpoint where (exactly) amyloid beta is made in the brain and periphery. I wish I could tell you more, but I suppose you shall just have to wait until my Nature or Neuroscience publication comes out. (Fingers crossed!) Until next time!
Image credit: Neuron.