Studying the cerebrospinal fluid of patients with Alzheimer’s disease may help determine the molecular subtype of the disease – molecular diagnostics

Image: Researchers have discovered different biological variants of Alzheimer’s disease (photo courtesy of 123RF)

Scientists have made an important discovery by identifying five different biological variants of Alzheimer’s disease, each of which potentially requires unique therapeutic approaches. This finding suggests that previously tested Alzheimer’s drugs may have been mistakenly considered ineffective or only mildly beneficial because these options were not taken into account.

Alzheimer’s disease is caused by the accumulation of amyloid and tau proteins in the brain. However, this aggregation is only one aspect of the complexity of the disease. Researchers, including those from the Amsterdam UMC (Amsterdam, the Netherlands), have used innovative methods to analyze additional biological processes associated with Alzheimer’s disease. These processes, including inflammation and nerve cell growth, were studied by measuring several biomarkers in the cerebrospinal fluid of patients who had amyloid and tau accumulations. In their analysis of cerebrospinal fluid from 419 people diagnosed with Alzheimer’s disease, the researchers assessed 1,058 proteins and identified five different biological subtypes of the disease. The first subtype is characterized by increased amyloid production, while the second shows an alteration of the blood-brain barrier, decreased amyloid production, and decreased neuronal growth.

These subtypes also show differences in protein synthesis, immune system function, and the functioning of the organ responsible for producing cerebrospinal fluid. Different subgroups within these variants have been found to have different rates of disease progression. This discovery has important implications for drug research against Alzheimer’s disease. A drug that is effective for one subtype of Alzheimer’s disease may not be effective for another. For example, a drug designed to reduce amyloid production may benefit patients with high amyloid production, but may be harmful to those with low levels. There is also the possibility that patients with a certain variant of Alzheimer’s disease may experience more side effects compared to patients with other variants. The researchers’ next goal is to demonstrate that these subtypes of Alzheimer’s disease do indeed respond differently to medications. This will pave the way for more personalized and effective treatments for Alzheimer’s disease in the future.

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Amsterdam CMC