Discovery of Three Molecular Subtypes Brings Us Closer to Unraveling Alzheimer’s Disease


There are many common elements in Alzheimer’s disease (AD), which is the most common type of dementia. It is now evident that there are varied spans of disease progression and responses to treatment.

Neuroscience News recently published findings from researchers at Mount Sinai’s Icahn School of Medicine. The study points to the fact that many people, in the early stages of AD, experience slow cognitive deterioration while others show a rapid decline. The same applies to loss of memory, psychosis, and depression.

Evidence of Subtypes

Dr. Bin Zang, the study’s lead author, points to the aforementioned differences indicating the existence of AD subtypes. He commented that there is a strong indication of molecular and biological factors influencing disease progression.

Three Major Subtypes Identified

The researchers relied on RNA sequencing to produce data that helped to identify three molecular subtypes. RNA and DNA, both genetic molecules, are similar in that they encode instructions to create proteins. RNA sequencing identifies the quantity of RNA in biological samples.

The team studied over 1,500 samples selected from hundreds of deceased AD patients’ five brain areas. A computational biology approach was used to show the relationships between RNA types, clinical traits, and biological factors driving AD’s progress.

As a result, three molecular AD subtypes were discovered. The subtypes were not associated with disease, stage, or age. They were replicated in various brain areas in two studies.

The three subtypes correlate with the multiple pathways that lead to degeneration of the brain.

Hallmarks of AD

Amyloid-beta plaque and tau neurofibrillary tangle, AD hallmarks, are found to be increased in specific molecular subtypes. Studies show that Alzheimer’s may be caused by an elevated immune response. And yet over 50% of AD brains analyzed do not show an increased immune response. The analysis of the samples did show, however, molecular drivers in the progression of AD.

The interaction between the AD lab animals and the molecular subtypes offers a partial explanation of why so many drugs that were tested successfully in animal models were unsuccessful in AD trials involving human participants. The explanation lies in the fact that participants carried varied molecular subtypes.

The researchers performed the subtyping post mortem and used brain tissue from patients. If in the future the team is able to validate these findings, that would bring about the identification of clinical features related to these molecular subtypes. It would also bring about earlier diagnosis and subsequent intervention leading to the practice of precision medicine for AD.

Check out the original study here.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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