Alzheimer's Tangles May Be Protective

The nerve tangles seen in the brains of people with Alzheimer's disease (AD) may not be the cause of the disease but rather a protective response to the disease, according to new findings by researchers at Case Western Reserve University School of Medicine (Cleveland, OH, USA).

The major component of neurofibrillary tangels (NFTs) is a protein called tau, which has undergone a biochemical reaction called phosphorylation. It has been assumed that NFTs are the cause of the progression to AD and nerve cell death. However, these tangles also occur in all brains with age, although there are a lot more in the brains of people with AD. Tau phosphorylation or fibril formation is unlikely to be the cause of neuronal death since NFT-bearing neurons appear to survive for decades. One study found that neurons containing NFTs can survive as long as 20 years.

There is growing evidence that oxidative stress is a significant factor in the development of AD. Free radicals and reactive oxygen species oxidize tissues. This damages membranes and DNA, disrupting normal cell function and leading to nerve cell death.

"Since oxidative stress is decreased in neurons bearing NFTs, we suspect that the accumulation of tau proteins might actually be a protective, antioxidant response that serves as a mechanism for cells to defend themselves,” explained senior author Mark A. Smith, Ph.D., professor of pathology at Case.

The fact that the embryonic neurons that survive after treatment with oxidants have increased tau phosphorylation relative to those that die further supports a protective role for tau phosphorylation. Also, NFT-like tau phosphorylation occurs during hibernation, which is a neuroprotective pnenomenon. The researchers also believe that amyloid-beta may be neuroprotective and may be an antioxidant. A paper explaining their position appeared in the April 2005 issue of Trends in Molecular Medicine.