Published on: June 22, 2012
by David Perlman for San Francisco Chronicle:
The mysterious proteins called prions, which build up in the human brain to cause Alzheimer’s and other dementias, are also linked to post-traumatic stress disorder in combat veterans and in the brain damage of athletes like football players who have suffered repeated concussions, UCSF researchers report.
These conclusions from a long, and at times controversial, research quest come from Nobel Prize-winning UCSF neurologist Stanley B. Prusiner and his colleagues at the medical center’s Institute for Neurodegenerative Disease in Mission Bay, where a difficult search for compounds that might block the prions is about to begin.
The brain diseases caused by prions include Alzheimer’s, Parkinson’s and Huntington’s, amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, and other varied disorders known collectively as the frontotemporal dementias, Prusiner said. Among those, he said, are the dementias suffered by some contact sport athletes, as well as “soldiers from the Iraq and Afghanistan wars.”
The findings, along with his account of discoveries he and other researchers have made over years of work, appear this week in the journal Science and the Proceedings of the National Academy of Sciences.
The path to the latest findings began more than 30 years ago, when Prusiner found that strange proteins capable of reproducing themselves were in the brains of fauna suffering from such deadly animal diseases as scrapie in sheep and mad cow disease, or bovine spongiform encephalopathy.
The same proteins were also responsible for an obscure hereditary human disorder called Creutzfeldt-Jakob disease, he maintained.
Typical of these disorders were clumps and tangles of the proteins apparently caused by other proteins. Prusiner named those proteins “prions,” for proteinaceous infective particles, and said they were the cause of the diseases. Today hundreds of researchers around the world are following the protein trail in varied brain diseases.
Now Prusiner has seen the symptoms of the “prion diseases” in former football players, retired boxers and military patients in psychiatric counseling for PTSD, all suffering the same symptoms: memory loss, mood swings, apathy and severe psychological problems.
The presence of prions in the brain is ordinarily normal, and Prusiner said Thursday he initially believed decades ago that when they were “mis-folded” into abnormal shapes, they became capable of duplicating themselves again and again until they caused brain disease.
Now he concludes, they are actually capable of multiplying in what he terms “alternative” shapes, with each shape responsible for a different type of dementia.
And like in the better-known dementias, Prusiner said, the abnormal prions in the brains of those athletes and war veterans are responsible for the formation of massive clumps of prion proteins called amyloid beta, and the long tangles of prion proteins called tau, both of which are the defining signs of Alzheimer’s. They are also present in the other dementias, he said.
Eric Kandel, a Nobel Prize-winning neuropsychiatrist at Columbia University, called Prusiner’s prion work “extremely profound.”
“His has been the creative vision and unifying insight that has made the field realize that these various degenerative diseases of the brain are protein mis-folding disorders of the prion type; a major step forward,” Kandel said in an e-mail.
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Two blood markers, phosphorylated tau 217 (p-tau217) and phosphorylated tau 181 (p-tau181), showed strong diagnostic performances for Alzheimer’s disease and discriminated Alzheimer’s from frontotemporal lobar denervation (FTLD) syndromes and normal cognition, a retrospective study...
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