Amyloid plaques are clumps of misfolded proteins that form in the spaces between nerve cells. These abnormally configured proteins are believed by brain researchers to play a key role in Alzheimer’s disease. The amyloid plaques first develop in the areas of the brain concerned with memory and other cognitive functions. 

The beta-amyloid protein involved in Alzheimer’s comes in several different molecular forms that collect between neurons. It is formed from the breakdown of a larger protein called amyloid precursor protein. One form, beta-amyloid 42, is thought to be especially toxic. 

Healthy nerve cells are supported internally by structures called microtubules that help guide nutrients and molecules from the cell body to the axon and dendrites. In healthy neurons, a protein named tau normally binds to and stabilizes microtubules. However, in Alzheimer’s disease, abnormal chemical changes cause tau to detach from microtubules and stick to other tau molecules, forming threads that eventually join to form tangles inside neurons. These tangles block the neuron’s transport system, which harms the synaptic communication between neurons.

Emerging evidence suggests that Alzheimer’s-related brain changes may result from a complex interplay among abnormal tau and beta-amyloid proteins and several other factors. It appears that abnormal tau accumulates in specific brain regions involved in memory. Beta-amyloid clumps into plaques between neurons. As the level of beta-amyloid reaches a tipping point, there is a rapid spread of tau throughout the brain.

While amyloid plaques are the hallmark of Alzheimer’s disease and other neurodegenerative diseases, it is still not clear if and how such plaques contribute to disease progression and its pathological implications.

Scientists at Ben-Gurion University (BGU) of the Negev in Beersheba are the first to show that amyloid fibrils made of the well-known “beta amyloid” protein catalyze the breakdown of neurotransmitters in the brain. They thus offer an alternative explanation on how the plaques “poison” the brain by breaking up important neurotransmitters such as dopamine and adrenaline.

This study offers an alternative explanation on how the plaques “poison” the brain by breaking up important neurotransmitters such as dopamine and adrenaline.

The study’s findings were just published in the prestigious peer-reviewed Chem Catalysis, a Cell Press journal, under the title “β-Amyloid fibrils catalyze neurotransmitter degradation.”

The research was led by chemistry department Prof. Raz Jelinek and doctoral student Elad Arad, in collaboration with Prof. Hanna Rapaport and Avigail Baruch Leshem. The researchers discovered remarkable catalytic activity that was directly caused by beta-amyloid fibrils, not non-fibril organizations of the protein). As neurotransmitter degradation has been observed in brains of Alzheimer’s disease patients, suggesting that the fibril-catalysis phenomenon discovered by Jelinek and colleagues may indeed be physiologically significant.

“Our findings open intriguing new avenues of research into the molecular factors in neurodegenerative diseases that could bring us closer to therapeutic treatments,” said Jelinek, who is vice president and dean of research & development at BGU.