Dutch Scientists Have Discovered Five Biological Variants of Alzheimer’s Disease

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Dutch researchers have discovered five distinct biological variants of Alzheimer’s disease, necessitating personalized treatment approaches. Their research underscores the importance of developing variant-specific drugs to enhance the effectiveness and safety of Alzheimer’s treatments.

Research from Amsterdam UMC may play a crucial role in assessing future medications.

Researchers in the Netherlands have identified five biological variants of Alzheimer’s disease, which may require different treatment. Consequently, drugs tested earlier might have seemed ineffective or only slightly effective. This finding was made by Betty Tijms and her team from the Alzheimer Center Amsterdam, Amsterdam UMC, and Maastricht University. Their study was recently published in the journal Nature Aging.

In those with Alzheimer’s disease, the amyloid and tau proteins clump in the brain. In addition to these clumps, other biological processes such as inflammation and nerve cell 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 the second type, the blood-brain barrier is disrupted and there is a reduced amyloid production and less nerve cell 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, a 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.

Reference: “Cerebrospinal fluid proteomics in patients with Alzheimer’s disease reveals five molecular subtypes with distinct genetic risk profiles” by Betty M. Tijms, Ellen M. Vromen, Olav Mjaavatten, Henne Holstege, Lianne M. Reus, Sven van der Lee, Kirsten E. J. Wesenhagen, Luigi Lorenzini, Lisa Vermunt, Vikram Venkatraghavan, Niccoló Tesi, Jori Tomassen, Anouk den Braber, Julie Goossens, Eugeen Vanmechelen, Frederik Barkhof, Yolande A. L. Pijnenburg, Wiesje M. van der Flier, Charlotte E. Teunissen, Frode S. Berven and Pieter Jelle Visser, 9 January 2024, Nature Aging.
DOI: 10.1038/s43587-023-00550-7

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