The present consensus on Alzheimer's disease focuses on the accumulation of misfolded proteins into amyloid plaques as the crucial mechanism, and thus clearing amyloid is a major research focus. Turning this focus into working therapies is taking far longer than expected, however, with numerous disappointing outcomes along the way so far. This state of affairs leads to a research environment in which other theories and approaches are multiplying, in search of better results. The example noted below is one of a great many initiatives that incorporate a quite different way of looking at the mechanisms of Alzheimer's disease:
The lipid Ceramide is pervasive throughout the human body as well as other animal and plant species. Researchers have identified elevated ceramide levels as a risk factor for Alzheimer's and have shown that amyloid triggers excess production of the lipid, although precisely how and why remain a mystery. That synergy had the scientists expecting that generating antibodies against ceramide would hamper plaque formation. Instead they found that the excessive ceramide had already worked its way into the bloodstream, generating antibodies that supported disease progression, particularly in female mice. This appears to support the theory that Alzheimer's is an autoimmune disease, which tends to be more common in women and is characterized by the immune system producing antibodies against a patient's tissue.
It also has researchers thinking that measuring blood levels of the lipid or some of its byproducts could be an early test for Alzheimer's since ceramide levels were elevated well before mice showed signs of substantial plaque formation. "It's a chicken-egg situation. We don't know if the anti-ceramide antibodies that may develop naturally during disease might be a result or a cause of the disease." The researchers are now circling back to a previous approach of directly blocking ceramide, this time, using a genetically engineered mouse that from birth lacks an enzyme needed to make ceramide, then crossbreeding it with an Alzheimer's mouse model. They expect that the mice genetically programmed to get Alzheimer's will produce less ceramide and less amyloid.