Fight Aging!

Alzheimer's research is comparatively well funded, but the production of therapies based on the presently dominant amyloid hypothesis is proving to be a hard, slow grind. The most promising involve directing the immune system to break down amyloid-β or related proteins, but even this line of work is a litany of failed early stage trials at this point. Since theorizing and preliminary investigation of new theories is a lot cheaper than contributing to the messy and very complicated late stage development of potential amyloid clearance treatments, a lot of theorizing is taking place. This is human nature at work; any faltering steps for the majority position in a field will lead to more work on alternative theories, even if it is just a matter of it being harder than expected to turn science into medicine in this case.

The failures haven't dented the primacy of amyloid and tau as targets: the consensus is that this is a hard problem, and the Alzheimer's research community is essentially having to build all of the technology and infrastructure to make immune therapies for clearance of misfolded proteins work at all, never mind work for amyloid. Still, Alzheimer's research is indistinguishable at the edges from general research into understanding the biochemistry of the brain. The pathology of Alzheimer's is entangled with the way in which the brain works in quite fundamental ways, and this is one of the reasons why this research is so well funded: it is driving much of the progress towards a greater understanding of neural biochemistry at all levels.

That is the background. Here I'll point out a couple of minority hypotheses on the causes and pathology of Alzheimer's disease. These are often quite interesting in and of themselves, such as the painkiller hypothesis, but you should probably take both of these papers with a grain of salt. All research has to be critically considered, and not just for the details of a specific paper - small sample size, possible errors, other interpretations that would also explain the data, and so forth - but also in the context of the bigger picture. Does it connect to other well-supported research? Does it stand alone, with no other groups looking into it? Being both alone and associated with a large and active field is usually not a good sign; it's a quiet rejection on the part of other researchers, who would otherwise comment, experiment, and write their own variant theories based on it.

Different Brain Regions are Infected with Fungi in Alzheimer's Disease

The possibility that Alzheimer's disease (AD) has a microbial aetiology has been proposed by several researchers. Here, we provide evidence that tissue from the central nervous system (CNS) of AD patients contain fungal cells and hyphae. Fungal material can be detected both intra- and extracellularly using specific antibodies against several fungi. Different brain regions contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi. Fungal infection is also observed in blood vessels, which may explain the vascular pathology frequently detected in AD patients. Sequencing of fungal DNA extracted from frozen CNS samples identifies several fungal species. Collectively, our findings provide compelling evidence for the existence of fungal infection in the CNS from AD patients, but not in control individuals.

Divalent Copper as a Major Triggering Agent in Alzheimer's Disease

Alzheimer's disease (AD) is at epidemic proportions in developed countries, with a steady increase in the early 1900 s, and then exploding over the last 50 years. This epidemiology points to something causative in the environment of developed countries. This paper will review the considerable evidence that that something could be inorganic copper ingestion. The epidemic parallels closely the spread of copper plumbing, with copper leached from the plumbing into drinking water being a main causal feature, aided by the increasingly common use of supplement pills containing copper.

Inorganic copper is divalent copper, or copper-2, while we now know that organic copper, or copper in foods, is primarily monovalent copper, or copper-1. The intestinal transport system, Ctr1, absorbs copper-1 and the copper moves to the liver, where it is put into safe channels. Copper-2 is not absorbed by Ctr1, and some of it bypasses the liver and goes directly into the blood, where it appears to be exquisitely toxic to brain cognition. Thus, while aggregation of amyloid-β has been postulated to be the cause of AD under current dogma, the great increase in prevalence over the last century appears to be due to ingestion of copper-2, which may be causing the aggregation, and/or increasing the oxidant toxicity of the aggregates.

An alternative hypothesis proposes that oxidant stress is the primary injuring agent, and under this hypothesis, copper-2 accumulation in the brain may be a causal factor of the oxidant injury. Thus, irrespective of which hypothesis is correct, AD can be classified, at least in part, as a copper-2 toxicity disease. It is relatively easy to avoid copper-2 ingestion, as discussed in this review. If most people begin avoiding copper-2 ingestion, perhaps the epidemic of this serious disease can be aborted.

Of course a great many things parallel the past century of economic development, not just copper plumbing. This is one of the problems with the painkiller hypothesis as well: near everything associated with wealth, technology, and progress has an upward curve that happens to correlate with Alzheimer's incidence.