In Alzheimer's, Aged "Railroad Tracks" Within Neurons May Impair Memory

One of the most common proteins within cells—which act as microscopic railroad tracks—may play a role in Alzheimer's disease, according to a new study by scientists at Columbia University Vagelos College of Physicians and Surgeons and other research institutions.

These cellular railroad tracks, known as microtubules, maintain cell shape and are required for the transport of cargo. The new study shows that microtubules become too stable during early stages of Alzheimer’s disease, and that alters neuronal activity and impairs memory.

The work, published in the current issue of the journal Brain, also points toward a novel strategy for treating Alzheimer’s disease and other neurodegenerative disorders.

Stable, but old, railroad tracks 

The researchers first noticed that neurons from people who had died from Alzheimer’s contained microtubules that were more aged than in neurons from individuals without the disease.

It is normal for neurons to have microtubules that are stable and long-lived to support cell structure, analogous to the bones that support our bodies. But for neurons to maintain functional connections with each other, a portion of these microtubules must remain young and dynamic.

Indeed, for the brain to form new memories, neurons must have a perfect mix of stable and dynamic microtubules. To create that perfect mix, neurons employ a means to rejuvenate or regenerate young, dynamic microtubules from older ones.

Effect of microtubules on neurons and memory

The researchers turned to mice to examine the effect of old and stable microtubules on neurons and memory.

By inhibiting the cycle of microtubule regeneration, the team created mice with more long-lived microtubules within their neurons. These animals displayed memory deficits and had fewer synapses (communication connections between neurons).

"This was very interesting to us, because it proved that it is enough to unbalance the microtubule regenerating cycle to create synaptic dysfunction," says Francesca Bartolini, PhD, associate professor of pathology & cell biology at Columbia University Vagelos College of Physicians and Surgeons and a senior author of the new paper.

“And perturbation of this cycle seems to be a hallmark of Alzheimer's disease.”

Bartolini and her collaborators now hope to develop compounds that will target the microtubule-modifying enzymes and restore their normal activity in Alzheimer's disease and other neurodegenerative conditions.