Healthy Dendritic Spines Confer Protective Effect Against Alzheimer’s

The shape, size, and number of dendritic spines in the brain could play a major role in whether someone gets Alzheimer’s disease, new research from the University of Alabama at Birmingham suggests. Dendritic spines are sub-units of neurons that act as the connector to other neurons.

The research team demonstrated, for the first time, that the presence of healthy dendritic spines had a protective effect against Alzheimer’s in people whose brains had proteins associated with the disease.

“One of the precursors of Alzheimer’s is the development in the brain of proteins called amyloid and tau, which we refer to as the pathology of Alzheimer’s. However, about 30 percent of the aging population have amyloid and tau buildup but never develop dementia. Our study showed that these individuals had larger, more numerous dendritic spines than those with dementia, indicating that spine health plays a major role in the onset of disease,”

said lead author Jeremy Herskowitz, Ph.D., assistant professor in the Department of Neurology, School of Medicine.

Synapse Loss A Culprit

Neurons send out long, thin dendritic spines in search of other neurons. When they connect, a synapse, or exchange of information between neurons, occurs. This is the basis for memory and learning.

“One obvious culprit in Alzheimer’s disease is the loss of dendritic spines and thus the loss of synapses. This would impair the ability to think, so the assumption has been that those without dementia had healthy spines and those with dementia did not. But no one had gone in to see if that was true,”

said Herskowitz, who is the Patsy W. and Charles A. Collat Scholar in Neuroscience.

Herskowitz’s team studied brain samples from patients at memory clinics at Emory University. The control group did not have the Alzheimer’s pathology of amyloid plaques and tau tangles and never developed dementia.

A second group had the Alzheimer’s pathology and progressed to the disease. The third group had the pathology, but no disease.

Dendritic Spine Density

The researchers took thousands of microscopy images of the subject brains. Those images were then turned into 3-D images using novel, exclusive software. This allowed the team to look more fully at the shape and dimensions of each image.

“We first noted that the control group had more dendritic spines than the group with Alzheimer’s, which matched beautifully with existing historical data,” Herskowitz said. “But we also saw that the group with Alzheimer’s pathology but no disease also had more spines than the Alzheimer’s group. In fact, they had roughly the same spine density as the control group. What is even more exciting is that the ‘pathology but no disease’ group had very long spines, longer than both the control group and the disease group.”

Herskowitz says the longer spines demonstrated great plasticity, or ability to move. This indicates that they could navigate around or through amyloid plaques or tau tangles in their efforts to connect with other neurons.

“This provides an explanation of why some people are cognitively resilient to Alzheimer’s disease, even if they possess the typical Alzheimer’s pathology,”

he said.

Potential Drug Target

Herskowitz says that the high plasticity and density of dendritic spines in this population could be genetic.

Another theory suggests that it could be the result of healthy lifestyle behaviours, such as good diet and exercise, which are known to be protective against dementia. It may be that the reason these behaviours are protective is that they help maintain spine health, plasticity and density.

The findings also offer a new target for slowing or preventing Alzheimer’s in the first place, Herskowitz says.

“This provides a target for drugs that would be designed to support and maintain dendritic spine health in an effort to rebuild neurons or prevent their loss,” he said. “This data suggests that rebuilding neurons is possible. And as we are better able to identify the increase of amyloid and tau early in the progression of the disease, even before symptoms arise, we might be able to one day offer a medication that can contribute to maintaining healthy dendritic spines in those with the Alzheimer’s pathology.”

Herskowitz credits the innovative 3-D imaging system used in the study to groundbreaking work done by UAB science and technology honors student Benjamin Boros.

Boros, B. D., Greathouse, K. M., Gentry, E. G., Curtis, K. A., Birchall, E. L., Gearing, M. and Herskowitz, J. H. (2017)
Dendritic spines provide cognitive resilience against Alzheimer’s disease
Ann Neurol., 82: 602–614. doi:10.1002/ana.25049

Image: dendritic spines of control group (Top). Middle shows spines of the ‘pathology without disease’ group”. Bottom shows Alzheimer’s disease group. Credit: University of Alabama at Birmingham