New methods to identify and characterize irregular forms of beta-amyloid to inform treatments for Alzheimer’s disease

Scientists believe that a buildup of beta-amyloid protein in the brain plays a key role in the death of neurons, which can lead to Alzheimer’s disease. Although most people develop certain beta-amyloid brain proteins as they age, researchers suspect that abnormal forms of this protein may be key to the development of Alzheimer’s disease.

Researchers at the University of Texas at Arlington have developed the first methods to identify and characterize all the various irregular forms of beta-amyloid, adding another valuable element to the search for the exact causes of Alzheimer’s disease. Their results are published in two studies in Scientific reports And Analytical and bioanalytical chemistry.

“Aberrant beta-amyloid proteins can change brain chemistry, creating a big problem when developing drugs and immunotherapies aimed at slowing the progression of Alzheimer’s disease,” said lead author Daniel W. Armstrong. of both papers and Distinguished Professor of Chemistry and Biochemistry at Welch. “Our research is the first to describe new methods for identifying and characterizing the various aberrant forms of beta-amyloid. This knowledge could bring us one step closer to stopping the progression of this dreaded disease.”

Abnormal forms of beta-amyloid, called epimers and isomers, are difficult to detect because they have the same mass and amino acid sequence as normal forms of the protein. The study in Scientific reportsco-authored by Armstrong and UTA graduate students Elizabeth R. Readel, Arzoo Patel, Joshua I. Putman and Siqi Du, showed that the best way to isolate beta-amyloid from the brain was through a technique known as immunoprecipitation.

Many Alzheimer’s drugs are monoclonal antibodies that bind to beta-amyloid proteins to remove them from the brain and slow the progression of dementia symptoms. However, this research indicated that these drugs may not bind as well to abnormal versions of amyloid beta cells, which could explain why they are not always effective in slowing the progression of the disease.

Meanwhile, the newspaper Analytical and bioanalytical chemistry showed that liquid chromatography-mass spectrometry, the most common way to detect isolated amyloid beta proteins, produces different signals for normal and aberrant forms of the protein. This makes current methods of identification and quantification unreliable unless properly corrected. This study was co-authored by Readel, Patel and graduate teaching assistant Umang Dhaubhadel.

“Together, these results are truly encouraging in our quest to better understand Alzheimer’s disease to find better ways to slow its progression and symptoms,” Armstrong said.