Brain mapping’s path to developing cure for Alzheimer’s

Alzheimer’s is a devastating neurodegenerative disease – now a new brain mapping technique might allow scientists to understand exactly how it progresses through the brain and enable individualised patient predictions.

Scientists mapping the progression of dementia in the brain have been trying to understand how it spreads – does the atrophy associated with Alzheimer’s and other forms of progressive dementia spread out from an original source, or does it use synaptic pathways in the brain to travel to other locations and set up additional fronts of attack.

After all, the received wisdom that Alzheimer’s was caused by clumps of amyloid plaques is already being questioned.

A new study by the University of California San Francisco set out to tackle this question by mapping frontotemporal dementia (FTD), a condition in which the frontal and temporal anterior lobes of the brain atrophy. This causes two types of symptoms: behavioural changes and language problems.

Longevity.Technology: FTD cannot be slowed, stopped or cured and is the most common form of dementia in people under 60 [1]. This research provides an insight into how the disease spreads and how its progression varies from patient to patient. This variability has been an obstacle to successful clinical trials, so by successfully mapping the disease’s progression, the journey to therapy has begun and will allow treatments to be developed, invested in and brought to market.

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The TRL score for the technology addressed in this article is: “Early proof of concept demonstrated in the laboratory.”

As lead author Dr Jesse Brown, commented: “Knowing how dementia spreads opens a window onto the biological mechanisms of the disease — what parts of our cells or neural circuits are most vulnerable. You can’t really design a treatment until you know what you’re treating [2].”

The study, the results of which were published in Neuron earlier this week, involved a group of 42 people who suffered from one of two subtypes of FTD having an MRI scan at the beginning of the study and another one about 12 months later. The researchers analysed the data to map the disease’s progression by comparing it with MRI brain scans of 75 healthy participants. The research team were able to create standardised maps of 175 different brain areas and the corresponding regions with which they communicated, working out the “patient-tailored epicentre” of brain degeneration and how the atrophy would spread. They found that the results supported the hypothesis that neurodegenerative diseases don’t spread evenly in all directions like a tumour; rather they leap from one part of the brain to another along the neuro-highways in the brain.

“It’s like with an infectious disease, where your chances of becoming infected can be predicted by how many degrees of separation you have from ‘Patient Zero’ but also by how many people in your immediate social network are already sick,” says Dr Brown [3].

He added: “Just like epidemiologists rely on models of how infectious diseases spread to develop interventions targeted to key hubs or choke points, neurologists need to understand the underlying biological mechanisms of neurodegeneration to develop ways of slowing or halting the spread of the disease.”

Co-author Dr William Seeley said: “We are excited about this result because it represents an important first step toward a more precision medicine type of approach to predicting progression and measuring treatment effects in neurodegenerative disease.”

Although the Alzheimer’s mapping method and associated predictions are not yet ready for clinical trial, the researchers hope that it will lead to improved metrics for evaluating therapies already entering clinical trials. Is there a potential crossover with Elon Musk’s Neuralink, with technology using the brain’s neural superhighways to beat disease and degeneration and bring us closer to Longevity? Fire up the satnav – exciting times are ahead!