Dementia: Unprecedented detail of brain damage revealed

Using extremely powerful cutting-edge technology, a new study shows in great detail how dementia with Lewy bodies affects synapses, the important connections between neurons.

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The new study reveals how dementia affects synapses (shown here). Synapses are 5,000 times thinner than a sheet of paper.

Lewy body dementia is the most widespread form of dementia after Alzheimer’s disease and vascular dementia, according to the National Institute on Aging (NIA). More than 1 million people in the United States are affected, estimate the NIA.

Lewy body dementia comes in two forms: Parkinson’s disease and dementia with Lewy bodies (DLB).

The new study — led by researchers at the University of Edinburgh in the United Kingdom, in collaboration with those at Universitat Autònoma de Barcelona (UAB) in Spain — focuses on the granular changes that occur in the brains of those affected by DLB.

Specifically, the researchers examined the impact of DLB on synapses — that is, the tiny spaces between neurons that facilitate electrical or chemical communication between brain cells. Synapses are crucial for memory formation.

The first author of the paper is UAB’s Martí Colom-Cadena, and the findings were published in the journal Brain.

As the authors explain, this is the first time that scientists have offered such detailed insights into the brain damage caused by DLB.

Toxic protein found in super-small synapses

It is a known fact that in DLB, clumps of a sticky protein called alpha-synuclein cause damage to the brain. But what wasn’t known — until now — was that these damaging clumps could form around the synapses.

Such a level of detail has been difficult to achieve so far because of a lack of appropriate microscopic technology.

In the study, Colom-Cadena and colleagues used a powerful technology called “array tomography” to study the ultra-narrow synapses. They applied this technology to study the brain tissues of five people who had died with DLB as well as to that of five healthy controls.

In all, the team analyzed 1,318,700 so-called pre- or post-synaptic terminals, or the two sides of the synapses. A synapse is between 20 and 40 nanometers, or up to “5,000 times smaller than the thickness of a sheet of paper.”

In DLB brain tissue, the researchers found “small aggregates” of alpha-synuclein on both sides of the synapses. This offers new insights into how brain damage occurs in DLB, as it suggests that the toxic protein might “jump” between neurons via synapses.

Findings could stop the damage from spreading

The scientists hope that the findings will bring us closer to developing new treatments for DLB.

“DLB is a devastating condition and our findings suggest that it is at least partly driven by damage to synapses,” says Prof. Tara Spires-Jones, program lead at the U.K. Dementia Research Institute at the University of Edinburgh, and one of the lead investigators of the study.

These discoveries should invigorate the search for therapies aimed at reducing synaptic damage and open the possibility of targeting the spread of alpha-synuclein through the brain, which could stop disease progression in its tracks.”

Prof. Tara Spires-Jones

Dr. Rosa Sancho, head of research at Alzheimer’s Research U.K., also comments on the findings, saying, “This exciting research using cutting-edge technology sheds new light on the progression of DLB in the brain.”

“The results,” adds Dr. Sancho, “provide convincing, measurable, and visual evidence that toxic alpha-synuclein is disrupting synapses that could potentially contribute to the devastating symptoms of the disease.”