Alzheimer’s spreads through linked nerve cells

Washington - Alzheimer’s disease and other forms of dementia may spread within nerve networks in the brain by moving directly between connected neurons, instead of in  other ways proposed by scientists, such as by propagating in all directions, results of a new study suggested.

The researchers behind the study were led by neurologist and MacArthur Foundation “genius award” recipient William Seeley, MD, from the UCSF Memory and Aging Center, and  post-doctoral fellow Helen Juan Zhou, PhD, now a faculty member at Duke-NUS Graduate Medical School in Singapore.

They concluded that a nerve region’s connectedness to a disease hot spot trumps overall connectedness, spatial proximity and loss of growth-factor support in predicting its vulnerability to  the spread of disease in some of the most common forms of dementia, including Alzheimer’s disease.

The finding, based on new magnetic resonance imaging research (MRI), raises hopes that physicians may be able to use MRI to predict the course of dementias – depending on where within  an affected network degenerative damage is first discovered – and that researchers may use these predicted outcomes to determine whether a new treatment is working.

Network modeling combined with functional MRI might serve as an intermediate biomarker to gauge drug efficacy in clinical trials before behavioral changes become measurable, according

to Seeley.

“Our next goal is to further develop methods to predict disease progression, using these models to create a template for how disease will progress in the brain of an affected individual,”

Seeley said.

“Already this work suggests that if we know the wiring diagram in a healthy brain, we can predict where the disease is going to go next. Once we can predict how the network will change

over time we can predict how the patient’s behaviour will change over time and we can monitor whether a potential therapy is working,” he stated.

The new evidence suggests that different kinds of dementias spread from neuron to neuron in similar ways, even though they act on different brain networks, according to Seeley.

Seeley’s previous work and earlier clinical and anatomical studies showed that the patterns of damage in the dementias are linked to particular networks of nerve cells, but until now

scientists have found it difficult to evaluate in humans their ideas about how this neurodegeneration occurs.

In the current study, the researchers modeled not only the normal nerve network that can be affected by Alzheimer’s disease, but also those networks affected by frontotemporal dementia

(FTD) and related disorders, a class of degenerative brain diseases identified by their devastating impact on social behaviours or language skills.

The scientists mapped brain connectedness in 12 healthy people. Then they used data from patients with the five different diseases to map and compare specific regions within the networks

that are damaged by the different dementias.

“For each dementia, we looked at four ideas that scientists often bring up to explain how dementia might target brain networks. The different proposed mechanisms lead to different

predictions about how a region’s place in the healthy network affects its vulnerability to disease,” Seeley explained

Details of the finding have been reported in the March 22 edition of the journal Neuron.