The research focused on the accumulation and spread of a toxic protein in the brain called tau. Alongside amyloid-beta, another protein known to be implicated in neurodegeneration, the spread of tau has been associated with the cognitive decline seen in Alzheimer’s.
Positron emission tomography (PET) imaging was used to monitor levels of tau, and patterns of spread, in the brains of over 1,000 subjects. The cohort spanned the spectrum of Alzheimer’s patients, from those yet to display symptoms of cognitive decline to those in advanced stages of dementia.
"In contrast to how we have so far interpreted the spread of tau in the brain, these findings indicate that tau pathology in the brain varies according to at least four distinct patterns,” says Jacob Vogel, lead author of the new study. “This would suggest that Alzheimer's is an even more heterogeneous disease than previously thought.”
The four variants of tau spread clearly corresponded with symptomatic experiences. These four variants were also quite evenly spread across the cohort meaning they all were common and there likely is no one single dominant type of Alzheimer’s disease.
Variant one was the most prevalent, detected in 33 percent of cases. This pattern of tau spread was primarily located in the temporal lobe and influenced memory.
Variant two, on the other hand, displayed greater tau spread in other parts of the cerebral cortex. Around 18 percent of cases showed this kind of spread and it manifested in difficulties with executive functions such as self-regulation and focus.
Variant three, the second-most prevalent subtype, was noted in 30 percent of cases. It showed distinct tau accumulations in the visual cortex. Symptoms of this variant included difficulties distinguishing distance, shapes, contours, and general orientation.
The final variant described in the study saw the asymmetric spread of tau across the left hemisphere of the brain. This mostly influenced language skills and was detected in 19 percent of cases.
"Because different regions of the brain are affected differently in the four subtypes of Alzheimer's, patients develop different symptoms and also prognoses,” notes Oskar Hansson, from Lund University and corresponding author on the study “This knowledge is important for doctors who assess patients with Alzheimer's, and it also makes us wonder whether the four subtypes might respond differently to different treatments.”
This is not the first research to divide Alzheimer’s disease into different subtypes. Currently, the disease is only classified as either early-onset Alzheimer's or late-onset Alzheimer's, and a milestone 2018 study presented six different disease categories based on specific cognitive and genomic characteristics.
A more recent brain tissue study divided the disease into three different molecular subtypes. However, until now it has been difficult to translate these findings into a potential diagnostic tool.
A strength of this new study is the way to takes an accessible brain-imaging tool and uses it to categorize tau accumulations alongside symptomatic presentation in a large number of patients. The researchers cautiously note follow-up work is needed to validate these patterns over longer periods of time, but it seems to be increasingly clear Alzheimer’s is a much more diverse disease that previously assumed.
“We now have reason to reevaluate the concept of typical Alzheimer's, and in the long run also the methods we use to assess the progression of the disease,” says Vogel.
The new study was published in the journal Nature Medicine.
Source: Lund University