Pathologically, there are three things that are always seen in brains affected by Alzheimer’s disease: amyloid plaque, hyperphosphorylated tau protein, and signs of inflammation. There is dramatic evidence that immunoexcitotoxicity can cause all three of these pathological effects in the brain.

Until recently, it was assumed that beta amyloid, the substance that forms amyloid plaque, was the cause of the brain degeneration associated with Alzheimer’s. But new evidence suggests that beta amyloid actually plays a lesser role, and that immunoexcitotoxicity is the primary mechanism of the disease.

Doctors have known for a long time that some elderly people can have extensive amyloid deposits in their brain, yet still have perfectly normal memory, orientation, and other cognitive functions. It’s the type of amyloid that makes a difference.

Alzheimer’s patients have a form of plaque that is especially inflammatory. But evidence suggests that something else is at play as well. Hyperphosphorylated tau protein — which is found inside the damaged neurons — plays a major role in Alzheimer’s. But it is a product of what is causing the disease, not the actual cause of the disease.

Tau protein is associated with neuron pathway function, so it is vital to brain function. When this protein is overphosphorylated, it begins to form clumps called neurofibrillary tangles. These block neuron pathways.

In 1982, researchers suggested that the herpes simplex type 1 (HSV-1) virus could be the cause of Alzheimer’s disease, based on a number of findings linking the two. In an unpublished study, they found that out of 70 human brains of people who died with Alzheimer’s disease, 67 contained evidence of HSV-1 infection within the same areas of the brain that were known to be affected by Alzheimer’s — the temporal cortex, frontal cortex, and the hippocampus.

In more recent studies, the same lead researcher (M.J. Ball) also found that the HSV-1 virus could remain sleeping (latent) in the trigeminal ganglion — a cranial nerve ganglion outside the brain. The virus could be periodically awakened, leading to bouts of inflammation within the infected parts of the brain.

We can distinguish between a long-term (latent) infection with HSV-1 and a reactivation of the virus using special antibody tests. The IgG test detects the sleeping virus; the IgM test signifies an awakened virus that is causing an acute infection. After the virus is awakened (reactivated), the IgM test remains positive for one to two months.

Ball and colleagues found that there was no link between being IgG positive for the virus and a higher risk of Alzheimer’s disease. Yet being positive for IgM increased the risk of developing Alzheimer’s disease by 255 percent.

Other researchers have found the same link to reactivation of the sleeping virus.