Different biological variants discovered in Alzheimer’s disease

Dutch scientists have discovered five biological variants of Alzheimer’s disease, which may require different treatments. As a result, previously tested medications may falsely appear to be ineffective or minimally effective. This is the conclusion of researcher Betty Tijms and her colleagues from the Alzheimer Center Amsterdam, UMC Amsterdam and Maastricht University. Their study is published in Natural aging.

In people with Alzheimer’s disease, amyloid and tau proteins clump together in the brain. In addition to these clumps, other biological processes such as inflammation and nerve cell growth are also involved. Using new techniques, researchers were able to measure these other processes in the spinal fluid of patients with amyloid and tau clumps.

Betty Tijms and Pieter Jelle Visser examined 1,058 proteins found in the spinal fluid of 419 people with Alzheimer’s disease. They found that there are five biological variants within this group. The first variant is characterized by increased production of amyloid. In a second type, the blood-brain barrier is disrupted, leading to reduced amyloid production and less nerve cell growth.

In addition, the variants differ in the degree of protein synthesis, the functioning of the immune system and the functioning of the organ that produces cerebrospinal fluid. Patients with different variants of Alzheimer’s disease also showed differences in other aspects of the disease. For example, researchers have seen faster disease progression in certain subgroups.

The results are of great importance for drug research. This could mean that a certain drug might only work on one variant of Alzheimer’s disease. For example, a drug that inhibits amyloid production may work in the variant with increased amyloid production, but may be harmful in the variant with decreased amyloid production. It is also possible that patients with one variant have a higher risk of side effects, whereas this risk would be much lower with other variants.

The next step for the research team is to show that Alzheimer’s disease variants do indeed respond differently to drugs, so that all patients can be treated with appropriate drugs in the future.

Provided by the University of Amsterdam Medical Center