The Spread of Neurodegenerative Disease

5.4 million Americans suffer from Alzheimers and 3 million from Parkinson's disease. Doctors who treat patients with these among other neurodegenerative conditions believe that the diseases are spreading though their patients' brains. The stages of both Alzheimers and Parkinson's disease show these pathological effects.

Until recently, only in prion disease had this spread been shown, resulting in proof that the agent of spread is the prion protein. More recently, however, the notion that other neurodegenerative diseases could spread through the movement of the pathognomonic disease proteins has been raised for beta amyloid (Aß), tau, and a-synuclein.

The first evidence that proteins other than prions could be pathologic was described in 1994, when the introduction of brain tissue from a patient with Alzheimer's disease into the brains of aged marmosets was followed by the seeding of Aß plaques. However, this report was largely ignored, partly because work in elderly primates is difficult and slow.

Studies in humans and experimental animal models have been complemented by the study of cells; both misfolded tau and misfolded a-synuclein can be taken up by cells and therein act as seeds, inducing the misfolding of the endogenous protein. The latter observations open the way to mechanistic experiments on the nature of the phenomena involved in templating.

Collectively, these studies, which provide strong support for the hypothesis that disease spread and templating are general phenomena in neurodegenerative disease, are relevant to the biology and epidemiology of Alzheimer's disease, Parkinson's disease, and frontotemporal dementia, as well as to new approaches to treatment. The extent to which the processes of spread within the brain are physiologic rather than strictly pathologic events is not clear. The process of spreading suggests that there are places at which therapies could be targeted. It also implies that stochastic disease may have its genesis in a single cell.

Source: New England Journal of Medicine May 2012