Proposing Alzheimer's to be Several Distinct Conditions
The research linked below isn't the first time scientists have proposed that what we currently call Alzheimer's disease is in fact a collection of different and distinct ways to end up with a similar end result. You might lump this in with other portions of the theorizing and exploration of alternatives that is taking place at least partially in reaction to the slow pace of progress towards working therapies based on the dominant amyloid hypothesis. The development of immunotherapies to clear amyloid is the current leading edge of that work, but trials have been disappointing to date. It may well be that this is simply because building a robust platform for immunotherapies targeting the brain is inherently challenging, rather than issues with amyloid as a target, but that hasn't stopped a great many competing hypotheses from emerging in the meanwhile.
Deciphering the mechanism that underlies the development of Alzheimer's disease in certain families but not in others, researchers have proposed that the malady is actually a collection of diseases that probably should be treated with a variety of different approaches. The late onset feature typical to distinct neurodegenerative diseases, and the common temporal emergence patterns of these maladies, raise key questions: first, why do individuals who carry disease-linked mutation show no clinical signs until their fifth or sixth decade of life? In addition, why do apparently distinct disorders share a common temporal emergence pattern? One possible explanation is that as people age, the efficiency of the mechanisms that protect younger people from the toxic aggregation of proteins declines, thus exposing them to disease. Indeed, previous studies clearly indicate that the aging process plays key roles in enabling neurodegenerative disorders to onset late in life.Since neurodegenerative disorders stem from aberrant protein folding, an international research team postulated that an aging-associated decline in the activity of proteins that assist other proteins to fold properly may be one mechanism that exposes the elderly to neurodegeneration. To identify such mechanisms, they searched for similar mutational patterns in different proteins that are linked to the development of distinct neurodegenerative disorders. Their research showed that the development of Alzheimer's disease in certain families, and of a familial prion disorder in other families, originate from very similar mutational patterns. Based on this discovery, they identified that the malfunction of the protein cyclophilin B, which helps nascent proteins to attain their proper spatial structures, is responsible for the manifestation of both maladies. They also comprehensively characterized the mechanism that underlies the development of Alzheimer's disease in individuals who carry these mutations, and found that it has no relevance to the emergence of the disease in patients who carry other Alzheimer's-linked mutations. "This study provides important new insights: first, it shows that the development of distinct neurodegenerative disorders stems from a similar mechanism. More importantly, it indicates that Alzheimer's disease can emanate from more than one mechanism, suggesting that it is actually a collection of diseases that should be classified."