New Insight Into How Alzheimer’s Begins

Summary: Researchers discover a way doctors can detect early signs of Alzheimer’s by looking at the back of patients’ eyes.

Source: UTMB.

A new study from The University of Texas Medical Branch at Galveston offers important insight into how Alzheimer’s disease begins within the brain. The researchers found a relationship between inflammation, a toxic protein and the onset of the disease. The study also identified a way that doctors can detect early signs of Alzheimer’s by looking at the back of patients’ eyes.

“Early detection of Alzheimer’s warning signs would allow for early intervention and prevention of neurodegeneration before major brain cell loss and cognitive decline occurs,” said lead author Ashley Nilson, a neuroscience graduate student. “Using the retina for detecting AD and other neurodegenerative diseases would be non-invasive, inexpensive and could become a part of a normal screening done at patient checkups.”

UTMB researchers have previously found evidence that a toxic form of tau protein may underlie the early stages of Alzheimer’s. Brain cells depend on tau protein to form highways for the cell to receive nutrients and get rid of waste. In some neurodegenerative diseases like Alzheimer’s, the tau protein changes into a toxic form called tau oligomers and begins clumping into neurofibrillary tangles. When this happens, molecular nutrients can no longer move to where they are needed and the oligomers produce toxic effects leading to the eventual death of the brain cells.

It’s becoming increasingly clear that inflammation within the brain plays an important role in Alzheimer’s development and progression. Inflammation and loss of connections between nerves within the brain happen before the formation of the tangles that are characteristic of this disease. It’s possible that the tau oligomers may be responsible for this inflammation.

In a recent paper in the Journal of Alzheimer’s Disease, UTMB’s research team detailed their investigation on the relationship between inflammation, toxic tau and Alzheimer’s onset by performing systematic analyses of brain and retina samples from people with Alzheimer’s and a mouse model of Alzheimer’s.

a blue brain.

UTMB researchers have previously found evidence that a toxic form of tau protein may underlie the early stages of Alzheimer’s.
NeuroscienceNews.com image is adapted from the UTMB press release.

The results demonstrated that the toxic tau may induce inflammation in Alzheimer’s. The toxic tau spreads between connected brain regions, which may initiate inflammation in these new regions. This situation can create a cycle of toxic tau, inflammation and cell death throughout the brain over time.

Beyond determining eye health and corrective lens prescriptions, having an eye exam can alert health care professionals of several different health conditions including diabetic complications, high cholesterol and high blood pressure. Now, UTMB researchers found that retina tissue that they studied can show evidence of toxic tau and inflammation.

“Our findings suggest that the degeneration of nerve cells due to chronic inflammation induced by the tau oligomers may be combated through the combination of anti-tau oligomer and anti-inflammatory therapeutics for the treatment of Alzheimer’s and related diseases,” said senior author Rakez Kayed, associate professor in the UTMB Department of Neurology. “Our is continuing to expand our understanding of neurodegenerative diseases.”

About this Alzheimer’s disease research article

The authors include a team of collaborative scientists and doctors including UTMB’s Kelsey English, Julia Gerson, T. Barton Whittle, C. Nicholas Crain, Judy Xue, Urmi Sengupta, Diana Castillo-Carranza, Wenbo Zhang and Praveena Gupta.

Funding: The work was supported by the UTMB Mitchell Center for Neurodegenerative Disease, the University of Texas System Neuroscience and Neurotechnology Research Institute and Retina Foundation and the National Institutes of Health.

Source: Donna Ramirez – UTMB
Image Source: NeuroscienceNews.com image is adapted from the UTMB press release.
Original Research: Full open access research for “Tau Oligomers Associate with Inflammation in the Brain and Retina of Tauopathy Mice and in Neurodegenerative Diseases” byNilson, Ashley N.; English, Kelsey C.; Gerson, Julia E.; Whittle, T. Barton; Crain, C. Nicolas; Xue, Judy; Sengupta, Urmi; Castillo-Carranza, Diana L.; Zhang, Wenbo; Gupta, Praveena; and Kayed, Rakez in Journal of Alzheimer’s Disease. Published online September 12 2016 doi:10.3233/JAD-160912

Cite This NeuroscienceNews.com Article
UTMB. “New Insight Into How Alzheimer’s Begins.” NeuroscienceNews. NeuroscienceNews, 18 November 2016.
<http://neurosciencenews.com/alzheimers-tau-progression-5554/>.
UTMB. (2016, November 18). New Insight Into How Alzheimer’s Begins. NeuroscienceNews. Retrieved November 18, 2016 from http://neurosciencenews.com/alzheimers-tau-progression-5554/
UTMB. “New Insight Into How Alzheimer’s Begins.” http://neurosciencenews.com/alzheimers-tau-progression-5554/ (accessed November 18, 2016).

Abstract

Tau Oligomers Associate with Inflammation in the Brain and Retina of Tauopathy Mice and in Neurodegenerative Diseases

It is well-established that inflammation plays an important role in Alzheimer’s disease (AD) and frontotemporal lobar dementia (FTLD). Inflammation and synapse loss occur in disease prior to the formation of larger aggregates, but the contribution of tau to inflammation has not yet been thoroughly investigated. Tau pathologically aggregates to form large fibrillar structures known as tangles. However, evidence suggests that smaller soluble aggregates, called oligomers, are the most toxic species and form prior to tangles. Furthermore, tau oligomers can spread to neighboring cells and between anatomically connected brain regions. In addition, recent evidence suggests that inspecting the retina may be a window to brain pathology. We hypothesized that there is a relationship between tau oligomers and inflammation, which are hallmarks of early disease. We conducted immunofluorescence and biochemical analyses on tauopathy mice, FTLD, and AD subjects. We showed that oligomers co-localize with astrocytes, microglia, and HMGB1, a pro-inflammatory cytokine. Additionally, we show that tau oligomers are present in the retina and are associated with inflammatory cells suggesting that the retina may be a valid non-invasive biomarker for brain pathology. These results suggest that there may be a toxic relationship between tau oligomers and inflammation. Therefore, the ability of tau oligomers to spread may initiate a feed-forward cycle in which tau oligomers induce inflammation, leading to neuronal damage, and thus more inflammation. Further mechanistic studies are warranted in order to understand this relationship, which may have critical implications for improving the treatment of tauopathies.

“Tau Oligomers Associate with Inflammation in the Brain and Retina of Tauopathy Mice and in Neurodegenerative Diseases” byNilson, Ashley N.; English, Kelsey C.; Gerson, Julia E.; Whittle, T. Barton; Crain, C. Nicolas; Xue, Judy; Sengupta, Urmi; Castillo-Carranza, Diana L.; Zhang, Wenbo; Gupta, Praveena; and Kayed, Rakez in Journal of Alzheimer’s Disease. Published online September 12 2016 doi:10.3233/JAD-160912

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