Altering the ?-amyloid protein could help diagnose Alzheimer's disease.

Altering the ?-amyloid protein could help diagnose Alzheimer’s disease.

The main hallmark of Alzheimer’s disease (AD) is the presence in the brain of plaques formed from accumulations of ?-amyloid protein. Detecting these plaques is essential for an accurate diagnosis of this degenerative neurological disorder, but there is currently no way of detecting the plaques in the brains of living patients.

Now, US researchers from the Mayo Clinic School of Medicine have designed a compound that binds to ?-amyloid plaques in the brain, making them visible by current medical imaging technology, such as magnetic resonance imaging (MRI).

The team knew that such a compound must specifically target ?-amyloid plaques, be non-toxic, able to pass through the blood-brain barrier, and show up on MRI scans. The compound is based on a non-toxic fragment of the ?-amyloid protein, consisting of the first 30 amino acid residues (A?30).

Building on earlier work on a slightly longer ?-amyloid fragment (A?40), the researchers made a number of chemical alterations to A?30 to provide it with other essential characteristics. In order to get it through the blood-brain barrier to target specifically the plaques, the team systematically replaced two amino acids - glutamic and aspartic acid - with amine-modified versions - glutamyl-4-aminobutane and asparagyl-4-aminobutane.

In order to make A?30 visible by MRI, the team attached diethyl-enetriaminepentaacetic acid anhydride and gadolinium to its N-terminal aspartic acid residue. The researchers tested the ability of this new compound to detect plaques in samples of human and mouse brain. They found that it could not only pass through the blood-brain barrier, but would accurately target and label plaques in human and mouse brain samples, allowing the plaques to show up on MRI scans.

The Mayo team is now testing the compound further by using MRI to identify ?-amyloid plaques in the brains of living mice.

Jon Evans