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Researchers Discover Where Earliest Signs of Alzheimer’s Occur in the Brain

Summary: Researchers report they have discovered where the earliest signs of Alzheimer’s may occur in the brain. Initial accumulation of Alzheimer’s associated amyloid beta was discovered in an important functional network, the default mode network.

Source: Lund University.

Researchers at Lund University in Sweden have for the first time convincingly shown where in the brain the earliest signs of Alzheimer’s occur. The discovery could potentially become significant to future Alzheimer’s research while contributing to improved diagnostics.

In Alzheimer’s, the initial changes in the brain occur through retention of the protein, β-amyloid (beta-amyloid). The process begins 10-20 years before the first symptoms become noticeable in the patient.

In Nature Communications, a research team headed by Professor Oskar Hansson at Lund University has now presented results showing where in the brain the initial accumulation of β-amyloid occurs. It is in the inner parts of the brain, within one of the brain’s most important functional networks – known as the default mode network.

“A big piece of the puzzle in Alzheimer’s research is now falling into place. We previously did not know where in the brain the earliest stages of the disease could be detected. We now know which parts of the brain are to be studied to eventually explain why the disease occurs”, says Sebastian Palmqvist, associate professor at Lund University and physician at Skåne University Hospital.

The default mode network is one of several networks, each of which has a different function in the brain. It is most active when we are in an awake quiescent state without interacting with the outside world, for example, when daydreaming. The network belongs to the more advanced part of the brain. Among other things, it processes and links information from lower systems.

The study, conducted in collaboration with Michael Schöll, associate senior lecturer at the University of Gothenburg, and William Jagust, professor at the University of California, is based on data from more than 400 people in the United States who have an increased risk of developing Alzheimer’s, and about as many participants from the Swedish research project, BioFINDER. The brain status of all the participants was monitored for two years, and compared to a control group without any signs of Alzheimer’s.

The difficulty of determining which individuals are at risk of developing dementia later in life, in order to subsequently monitor them in research studies, has been an obstacle in the research world. The research team at Lund University has therefore developed a unique method to identify, at an early stage, which individuals begin to accumulate β-amyloid and are at risk.

Image shows a brain.

The default mode network is one of several networks, each of which has a different function in the brain. It is most active when we are in an awake quiescent state without interacting with the outside world, for example, when daydreaming. The network belongs to the more advanced part of the brain. Among other things, it processes and links information from lower systems. NeuroscienceNews.com image is in the public domain.

The method combines cerebrospinal fluid test results with PET scan brain imaging. This provides valuable information about the brain’s tendency to accumulate β-amyloid.

In addition to serving as a roadmap for future research studies of Alzheimer’s disease, the new results also have a clinical benefit:

“Now that we know where Alzheimer’s disease begins, we can improve the diagnostics by focusing more clearly on these parts of the brain, for example in medical imaging examinations with a PET camera”, says Oskar Hansson, professor at Lund University, and medical consultant at Skåne University Hospital.

Although the first symptoms of Alzheimer’s become noticeable to others much later, the current study shows that the brain’s communication activity changes in connection with the early retention of β-amyloid. How, and with what consequences, will be examined by the research team in further studies.

About this neuroscience research article

Funding: The current study was funded by the European Research Council (ERC), the Swedish Research Council (VR), the Swedish Alzheimer’s Foundation and Region of Skåne (through ALF funding).

Source: Oskar Hansson – Lund University
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity” by Sebastian Palmqvist, Michael Schöll, Olof Strandberg, Niklas Mattsson, Erik Stomrud, Henrik Zetterberg, Kaj Blennow, Susan Landau, William Jagust & Oskar Hansson in Nature Communications. Published online October 31 2017 doi:10.1038/s41467-017-01150-x

Cite This NeuroscienceNews.com Article
Lund University “Researchers Discover Where Earliest Signs of Alzheimer’s Occur in the Brain.” NeuroscienceNews. NeuroscienceNews, 1 November 2017.
<http://neurosciencenews.com/alzheimers-early-signs-7849/>.
Lund University (2017, November 1). Researchers Discover Where Earliest Signs of Alzheimer’s Occur in the Brain. NeuroscienceNews. Retrieved November 1, 2017 from http://neurosciencenews.com/alzheimers-early-signs-7849/
Lund University “Researchers Discover Where Earliest Signs of Alzheimer’s Occur in the Brain.” http://neurosciencenews.com/alzheimers-early-signs-7849/ (accessed November 1, 2017).

Abstract

Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity

It is not known exactly where amyloid-β (Aβ) fibrils begin to accumulate in individuals with Alzheimer’s disease (AD). Recently, we showed that abnormal levels of Aβ42 in cerebrospinal fluid (CSF) can be detected before abnormal amyloid can be detected using PET in individuals with preclinical AD. Using these approaches, here we identify the earliest preclinical AD stage in subjects from the ADNI and BioFINDER cohorts. We show that Aβ accumulation preferentially starts in the precuneus, medial orbitofrontal, and posterior cingulate cortices, i.e., several of the core regions of the default mode network (DMN). This early pattern of Aβ accumulation is already evident in individuals with normal Aβ42 in the CSF and normal amyloid PET who subsequently convert to having abnormal CSF Aβ42. The earliest Aβ accumulation is further associated with hypoconnectivity within the DMN and between the DMN and the frontoparietal network, but not with brain atrophy or glucose hypometabolism. Our results suggest that Aβ fibrils start to accumulate predominantly within certain parts of the DMN in preclinical AD and already then affect brain connectivity.

“Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity” by Sebastian Palmqvist, Michael Schöll, Olof Strandberg, Niklas Mattsson, Erik Stomrud, Henrik Zetterberg, Kaj Blennow, Susan Landau, William Jagust & Oskar Hansson in Nature Communications. Published online October 31 2017 doi:10.1038/s41467-017-01150-x

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