Researchers at the Icahn School of Medicine in Mount Sinai (New York, USA) have identified three main molecular subtypes of Alzheimer’s disease using RNA sequencing data, Which is a DNA-like genetic molecule that encodes instructions for producing proteins.
The work is advancing in our understanding of the mechanisms of Alzheimer’s disease and could pave the way for development of new and personalized therapies as it is the most common form of dementia, but it is quite diverse in its biological and pathological manifestations.
Currently, There is growing evidence that disease progression and responses to interventions differ significantly among Alzheimer’s patients. Some patients have slow cognitive impairment, while others the impairment is faster; some have significant memory loss and an inability to remember new information, while others do not; and some patients experience psychosis and / or depression associated with the disease, while others do not.
“These differences strongly suggest that there are subtypes of Alzheimer’s disease with different biological and molecular factors that drive disease progression, ”notes Bin Zhang, lead author of the study.
The work, published in Science Advances, looked at RNA sequencing data from more than 1,500 samples in five brain regions of hundreds of dead patients and through routine controls, and identified three main molecular subtypes of Alzheimer’s disease. These subtypes were identified regardless of age and stage of the disease, and were replicated in multiple brain regions in two cohort studies.
Objective: Precision medicine for Alzheimer’s
these subtypes correspond to different combinations of multiple deregulated biological pathways leading to brain degeneration. Tau neurofibrillary tangle and beta-amyloid plaque, two neuropathological features of Alzheimer’s, increase significantly only in certain subtypes.
“Our systematic identification and characterization of robust molecular subtypes of Alzheimer’s Disease reveal many new deregulated signaling pathways in the disease and point to new targets. These findings lay the groundwork for determining more effective biomarkers for early prediction of Alzheimer’s, studying causal mechanisms, developing next-generation therapies, and designing more effective and specific clinical trials that ultimately lead to precision medicine for Alzheimer’s disease. Future challenges in terms of research include replication of findings in larger cohorts, validation of specific subtype targets and mechanisms, identification of peripheral biomarkers, and clinical features associated with these molecular subtypes, ”concludes Dr. Zhang .