Dutch scientists uncover five different biological variants of Alzheimer's disease

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Dutch scientists have discovered five biological variants of Alzheimer's disease, which may require different treatment. As a result, previously tested drugs may incorrectly appear to be ineffective or only minimally effective. This is the conclusion of researcher Betty Tijms and colleagues from Alzheimer Center Amsterdam, Amsterdam UMC and Maastricht University. The research results will be published on 9 January in Nature Aging.

In those with Alzheimer's disease, the amyloid and tau protein clump in the brain. In addition to these clumps, other biological processes such as inflammation and nerve cells growth are also involved. Using new techniques, the researchers have been able to measure these other processes in the cerebrospinal fluid of patients with amyloid and tau clumps.

Betty Tijms and Pieter Jelle Visser examined 1058 proteins in the cerebrospinal 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 amyloid production. In a second type, the blood-brain barrier is disrupted and there is a reduced amyloid production and less nerve cells growth. Furthermore, 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 Alzheimer's variants also showed differences in other aspects of the disease. For example, the researchers found a faster course of the disease in certain subgroups.

The findings are of great importance for drug research. It means that a drug could only work in one variant of Alzheimer's disease. For example, medication 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, while that risk is much lower with other variants. The next step for the research team is to show that the Alzheimer's variants do indeed react differently to medicines, so that we can treat everyone with appropriate medicines in the future.

Journal reference:

Tijms, B. M., et al. (2024). Cerebrospinal fluid proteomics in patients with Alzheimer’s disease reveals five molecular subtypes with distinct genetic risk profiles. Nature Aging. doi.org/10.1038/s43587-023-00550-7.


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