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Newly discovered type of dementia may account for 20 percent of cases

Newly discovered type of demen...
Quadruple misfolded proteins, or QMP, refers to the presence of four separate kinds of toxic protein accumulations
Quadruple misfolded proteins, or QMP, refers to the presence of four separate kinds of toxic protein accumulations
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Quadruple misfolded proteins, or QMP, refers to the presence of four separate kinds of toxic protein accumulations
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Quadruple misfolded proteins, or QMP, refers to the presence of four separate kinds of toxic protein accumulations

Scientists are already struggling to make headway in the fight against dementia, and the discovery of a new more aggressive form of neurodegeneration that's often misdiagnosed as Alzheimer's disease further complicates the problem.

A new study from the University of Kentucky has described a novel form of dementia characterized by the toxic accumulation of four different proteins in the brain. The research suggests many patients diagnosed with Alzheimer’s disease may be suffering from this different, and more complex, neurodegenerative condition.

Alzheimer’s disease is generally defined by a damaging build-up of two kinds of proteins in the brain: amyloid-beta into plaques, and tau into neurofibrillary tangles. Almost every treatment developed in recent years to try and halt, or reverse, the accumulation of these toxic proteins has failed in human trials, and many researchers have looked to novel hypotheses to try and better understand the origins of Alzheimer’s.

Last year a landmark study described a novel form of dementia based on the abnormal aggregation of a protein called TDP-43. The disease was named limbic-predominant age-related TDP-43 encephalopathy, or LATE, and the researchers suggested about 20 percent of Alzheimer’s cases may actually be misdiagnosed LATE cases.

"One of the things that we've learned in the last decade or so is that a lot of people that we think have dementia from Alzheimer's disease, actually don’t,” explains Eric Abner, one of the lead researchers on the new University of Kentucky study. “There are other brain diseases that cause the same kind of symptoms as Alzheimer's, including some that we only recently figured out existed.”

The new study examined brain autopsy data from 375 subjects enrolled in a long-term project called the University of Kentucky Alzheimer's Disease Center Brain Bank. All the subjects donating brain tissue were closely followed for more than a decade before their death.

The researchers looked at accumulations of not only amyloid-beta, tau and TDP-43, but also alpha synuclein, a protein known to aggregate into toxic structures called Lewy bodies. These Lewy bodies are the primary pathological cause of Parkinson’s disease neurodegeneration.

The results revealed around 20 percent of all subjects with dementia at their time of death showed signs of accumulating all four kinds of toxic proteins. And those with all four of these pathologies displayed the most severe symptoms of dementia.

"They had every neurodegeneration causing pathology that we know about. There was not a name for this, so we came up with one: quadruple misfolded proteins, or QMP," says Abner.

Those individuals with QMP were seen to progress from mild cognitive impairment (MCI) to dementia at a faster rate than subjects with three or fewer pathologies. It is unclear exactly how these four pathological characteristics interact with one another, but the researchers note the autopsy data suggests amyloid-beta aggregations may precede the abnormal accumulations of the other three proteins. Whether this means amyloid plaques actively stimulate the subsequent accumulations of other proteins is not known at this stage.

Abner says his team’s findings complicate Alzheimer’s research by suggesting treatments focusing on just one of these pathologies may not account for the other degenerative processes that seem to be at play in dementia-related disease. First LATE and now QMP, these new categories of dementia are increasingly making it clear late-life cognitive decline, and its associated diseases, are more diverse than previously thought.

"This is not great news, because it means that even if we could completely cure Alzheimer's disease, we still have to deal with TDP-43 and alpha synuclein, and they are common in old age,” says Abner. “But, we have to understand exactly what we are up against as we try to stop dementia. We still have so much to learn.”

The new study was published in the journal JAMA Neurology.

Source: University of Kentucky via MedicalXpress

2 comments
paul314
So is this one kind of dementia, or simply multiple kinds attacking the same patient (the way it's possible to have heart disease *and* high blood pressure *and* diabetes at the same time)?
Karmudjun
Rich - well written and pretty well explained. Most of us knew that the dementia we diagnose and treat don't present the same in each person. We know that multiple organ systems impact the brain and can compound or minimize the "expression" of dementia in patients. One study in Cincinnati Ohio of some Catholic Nuns has resulted in our rethinking the process that leads to Alzheimers. Teasing out what actually causes the symptoms of the 5 types of dementia whether it is Lewy body, vascular, frontotemporal, alzheimers, and mixed dementia is not easy, but adding two more possibilities - "LATE" dementia and QMP will only confuse patient's families as well as med students. Families understand early & late dementia to mean stages of dementia. I'm afraid QMP will be as clear as mad cow disease - the prion neurological disorder that has biochemists baffled at this time. I do appreciate your thorough synopsis of this article, it shows that while we have approaches that help with memory and functioning in dementia patients, we don't have cures or even answers - but we are discovering more about the cellular degradation that frequently presents certain symptoms. Like Paul314 glibly stated - CVD, HTN, & DM can all appear in one patient; once we can target the specific pathways of disease in the brain the same way we target renal, pancreatic, and atherosclerotic processes for HTN, DM, and CVD, we may see some dementia patients surviving with a much better quality of life - which is our aim when we cannot cure.