Recent research reveals individual differences in brain tissue obtained from two patients with Alzheimer’s disease who had distinct clinical histories and severity of brain damage. Alzheimer’s disease is a progressive, irreversible brain disease that destroys memory and thinking skills. Many changes take place in the brain of a person with Alzheimer’s disease. Some of these changes can be observed in brain tissue by using microscopy after death. A common abnormality evident in the brains of people who have died with the disorder is the amyloid plaque. The plaques consist predominantly of abnormal deposits of a protein fragment called beta-amyloid or β-amyloid, frequently abbreviated as Aβ. The molecular architecture of Aβ aggregates that develop in human brain tissue has not been characterized in detail, but scientiic findings to date suggest that structural variations may be biomedically important.
For the first time, scientists precisely characterized the molecular structures of Aβ fibrils that form in the brains of patients with Alzheimer’s disease. Using sophisticated biophysical techniques, a single-length predominant fibril structure was recovered from each patient; however, the fibrils were structurally different from each other. These data suggest that brain fibrils appear first at a single site and then spread to other locations in the brain while retaining their respective identical structural signatures. The study further suggests that certain fibril structures may be more likely to cause and/or influence the severity of Alzheimer’s disease. The development of imaging agents that speciically target individual fibril structures will improve the reliability and specificity of diagnosis.
Lu J-X, Qiang W, Yau W-M, Schwieters CD, Meredith SC, and Tycko R. Molecular structure of β-amyloid fibrils in
Alzheimer’s disease brain tissue. Cell 154: 1257-1268, 2013.