Study shows different types of fibril formation correlating with Alzheimer's sub-types

January 5, 2017 by Bob Yirka report
Diagram of the brain of a person with Alzheimer's Disease. Credit: Wikipedia/public domain.

(Medical Xpress)—A team of researchers working at the National Institutes of Health in the U.S. and the University College London Institute of Neurology in the U.K. has found what appears to be a correlation between fibril formation types in the brain and Alzheimer's subtypes. In their paper published in the journal Nature, the team describes their examination of the brains of deceased Alzheimer's patients and what they found by comparing amyloid-beta peptide deposits with progression types.

One of the physical hallmarks of Alzheimer's disease is the development of amyloid-beta peptide deposits in brain tissue leading to the creation of fibrils. Prior research has shown that such fibrils in patients can vary in shape and size between people to the degree that subtypes have been identified. In this new effort, the researchers sought to find out if certain subtypes could be associated with certain types of disease progression—in this case, rapidly progressive and posterior cortical atrophy, which causes problems with visual processing.

To learn more, the researchers obtained 37 brain samples from 18 deceased Alzheimer's patients, some of whom had been diagnosed with typical symptoms, some with rapid progression and some with posterior cortical atrophy, and then compared the types of fibrils found (using solid-state NMR spectroscopy) with the three progression types—a very labor intensive, year-long process, which is why the sample numbers were low. In so doing, they found that patients with typical symptoms and those with posterior cortical atrophy had similar fibril formations in their brains, whereas those with rapidly progressive Alzheimer's had fibrils that were not only different from those with typical symptoms, but from others with the same progressive condition.

The researchers suggest their findings indicate that fibril subtypes can be correlated with progression types in patients with Alzheimer's disease, and that there might be different processes involved in fibril formation. However, they note the mechanism responsible for the differences is still unknown. They also suggest that as more is learned about Alzheimer's subtypes, new customized diagnostic tests and therapies might be developed to target specific kinds of fibril formations, helping to slow the progression of the still incurable disease for regardless of their progression type.

Explore further: Alzheimer's patients show striking individual differences in molecular basis of disease

More information: Wei Qiang et al. Structural variation in amyloid-β fibrils from Alzheimer's disease clinical subtypes, Nature (2017). DOI: 10.1038/nature20814

Abstract
Aggregation of amyloid-β peptides into fibrils or other self-assembled states is central to the pathogenesis of Alzheimer's disease. Fibrils formed in vitro by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, with variations in molecular structure that depend on fibril growth conditions. Recent experiments suggest that variations in amyloid-β fibril structure in vivo may correlate with variations in Alzheimer's disease phenotype, in analogy to distinct prion strains that are associated with different clinical and pathological phenotypes. Here we investigate correlations between structural variation and Alzheimer's disease phenotype using solid-state nuclear magnetic resonance (ssNMR) measurements on Aβ40 and Aβ42 fibrils prepared by seeded growth from extracts of Alzheimer's disease brain cortex. We compared two atypical Alzheimer's disease clinical subtypes—the rapidly progressive form (r-AD) and the posterior cortical atrophy variant (PCA-AD)—with a typical prolonged-duration form (t-AD). On the basis of ssNMR data from 37 cortical tissue samples from 18 individuals, we find that a single Aβ40 fibril structure is most abundant in samples from patients with t-AD and PCA-AD, whereas Aβ40 fibrils from r-AD samples exhibit a significantly greater proportion of additional structures. Data for Aβ42 fibrils indicate structural heterogeneity in most samples from all patient categories, with at least two prevalent structures. These results demonstrate the existence of a specific predominant Aβ40 fibril structure in t-AD and PCA-AD, suggest that r-AD may relate to additional fibril structures and indicate that there is a qualitative difference between Aβ40 and Aβ42 aggregates in the brain tissue of patients with Alzheimer's disease.

Related Stories

Alzheimer's patients show striking individual differences in molecular basis of disease

September 12, 2013
Alzheimer's disease is thought to be caused by the buildup of abnormal, thread-like protein deposits in the brain, but little is known about the molecular structures of these so-called beta-amyloid fibrils. A study published ...

Alzheimer fibrils at atomic resolution

August 4, 2016
Elongated fibres (fibrils) of the beta-amyloid protein form the typical senile plaque present in the brains of patients with Alzheimer's disease. A European research team, working in conjunction with a team from the United ...

Amyloid formation may link Alzheimer disease and type 2 diabetes

February 17, 2015
The pathological process amyloidosis, in which misfolded proteins (amyloids) form insoluble fibril deposits, occurs in many diseases, including Alzheimer disease (AD) and type 2 diabetes mellitus (T2D). However, little is ...

New research offers 'critical insights' for treating, preventing Alzheimer's disease

September 16, 2016
New research led by Northeastern University suggests that Alzheimer's disease may not progress like falling dominoes, as conventional wisdom holds, with one molecular event sparking the formation of plaques throughout the ...

Evidence for a remarkable structural diversity of amyloid fibrils in human and animal tissue

March 15, 2016
Formation of amyloid fibrils is a characteristic feature of neurogenerative diseases like Alzheimer's. As published in the journal Angewandte Chemie, German and American scientists have found evidence that these fibrils adopt ...

Recommended for you

Personality changes don't precede clinical onset of Alzheimer's, study shows

September 21, 2017
For years, scientists and physicians have been debating whether personality and behavior changes might appear prior to the onset of Alzheimer's disease and related dementias.

Newly ID'd role of major Alzheimer's gene suggests possible therapeutic target

September 20, 2017
Nearly a quarter century ago, a genetic variant known as ApoE4 was identified as a major risk factor for Alzheimer's disease—one that increases a person's chances of developing the neurodegenerative disease by up to 12 ...

Is the Alzheimer's gene the ring leader or the sidekick?

September 15, 2017
The notorious genetic marker of Alzheimer's disease and other forms of dementia, ApoE4, may not be a lone wolf.

Potential noninvasive test for Alzheimer's disease

September 6, 2017
In the largest and most conclusive study of its kind, researchers have analysed blood samples to create a novel and non-invasive way of helping to diagnose Alzheimer's disease and distinguishing between different types of ...

Researchers unlock the molecular origins of Alzheimer's disease

September 6, 2017
A "twist of fate" that is minuscule even on the molecular level may cause the development of Alzheimer's disease, VCU researchers have found.

Is dementia declining among older Americans?

September 5, 2017
(HealthDay)—Here's some good news for America's seniors: The rates of Alzheimer's and other forms of dementia have dropped significantly over the last decade or so, a new study shows.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.