A large team of researchers has developed a new way to classify patients with Alzheimer’s disease, suggesting we should think of the disease as six distinctly different conditions instead of one single disease.

Currently Alzheimer’s disease is only really separated into two types, either early-onset Alzheimer’s or late-onset Alzheimer’s, depending on what stage of a person’s life they begin displaying symptoms. However some researchers believe Alzheimer’s disease may be much more complicated and specific than that.

A new study is suggesting this homogenizing of a variety of different cognitive symptoms into one single diagnosis may be the reason behind the recent parade of failed clinical trials into Alzheimer’s drugs that were proving promising in early research.

“Alzheimer’s, like breast cancer, is not one disease,” says Shubhabrata Mukherjee, lead author on the new study. “I think a good drug might fail in a clinical trial because not all the subjects have the same kind of Alzheimer’s.”

In order to investigate potential cognitive and biological differences, the researchers first evaluated data comprising over 4000 patients diagnosed with late-onset Alzheimer’s. Cognitive scores were produced in relation to four different domains – language, memory, executive functioning and visuospatial functioning. From those scores the researchers placed all the subjects into six different groups.

The largest subgroup, comprising around 39 percent of subjects, displayed similar scores across all four cognitive domains, and the second largest subgroup, at 27 percent, displayed similar average scores except on memory, which revealed significantly lower numbers. This means that particular subgroup displayed greater memory impairment than other Alzheimer’s subjects. Other more smaller subgroups displayed greater impairment in specific cognitive domains, and 6 percent of subjects revealed two domains with substantially lower scores than others.

The next part of the study set out to investigate genome-wide genetic data to find out whether there were distinct biological differences between the subgroups. Substantial genetic variations were clearly identified between all six subgroups. The researchers discovered 33 different locations across the genome that could be clearly associated with single cognitive domain subgroups.

“The implications are exciting,” says Paul Crane, corresponding author on the research. “We have found substantial biological differences among cognitively defined subgroups of Alzheimer’s patients.”

The team hopes the research can act as a bouncing off point for a new way of thinking about Alzheimer’s disease. By understanding the disease as six different conditions, each with its own unique cognitive and biological fingerprint, there may be a way forward not only for more personalized treatments tailored to individual patients, but more effective and better targeted clinical trials.

The study involving 19 researchers from various institutions was published in the journal Molecular Psychiatry.

Source: UW Medicine

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