Nav: Home

A new biomarker of brain inflammation in early-stage Alzheimer's disease

March 03, 2016

Heidelberg, 3 March 2016 - Researchers at the Ludwig-Maximilians-University, the German Center for Neurodegenerative Diseases (DZNE), and the Institute for Stroke and Dementia Research (ISD) in Munich, Germany, have identified a brain inflammation marker in patients at early asymptomatic stages of Alzheimer's disease. This secreted marker molecule, which can be measured from cerebrospinal fluid taps, may provide clinicians with a rapidly detectable biomarker for the transition from preclinical Alzheimer's disease to cognitive impairment and progression to full dementia. Such is the conclusion of a multi-center study on a large group of human patients, published online in EMBO Molecular Medicine.

Alzheimer's disease, an increasing problem in today's aging populations, is characterized by amyloid peptide plaques and tau protein aggregates in nerve cells. Understanding its molecular causes and risk factors has been challenging because most cases develop sporadically without inherited genetic mutations, and because of the gradual progression of symptoms over the course of disease. Recognizing affected individuals early would be important for increasing treatment options and facilitating clinical trials of new therapeutics. However, the currently available preclinical diagnostics based on amyloid peptide and tau protein forms in the cerebrospinal fluid are not sufficiently specific, as individuals exhibiting them may still retain normal cognitive capabilities for years before developing dementia.

In the present work, the teams led by Michael Ewers (ISD) and EMBO Member Christian Haass (DZNE) focussed on the TREM2 protein, which functions in specialized brain immune cells called microglia that clear toxic material resulting from nerve cell injury. Microglia are activated during Alzheimer's disease progression and may mediate an initially protective inflammatory response, a notion that is also supported by epidemiological studies linking mutations in the TREM2 gene to increased risk of Alzheimer's and other neurodegenerative diseases. Conducting a cross-sectional study of a large cohort of patients with different levels of cognitive impairment and different disease stages, the researchers found that the amounts of a TREM2 fragment in the cerebrospinal fluid were highest during early stages characterized by mild cognitive impairment symptoms. Its levels declined again in late-stage patients with full dementia, closely mirroring the pattern of microglia activity during the course of the disease. Together, these findings indicate that microglia-mediated brain inflammation may demarcate the transition from preclinical Alzheimer's disease to full dementia.

"We now have the first marker for the capacity of brain immune cells to remove toxic materials," says Haass, "and its increase long before full Alzheimer's dementia shows that there is early neuronal injury that does not yet affect memory, but already triggers a microglia response." And Ewers adds, "If this response is indeed protective, then therapeutically modulating the activity of microglia could be beneficial in late-stage Alzheimer's patients as well as other brain disorders."
-end-
Read the article:

sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer's Disease and associate with neuronal injury markers

Suárez-Calvet M, Kleinberger G, Caballero MA, Brendel M, Rominger A, Alcolea D, Fortea J, Lleó A, Blesa R, Gispert JD, Sánchez-Valle R, Antonell A, Rami L, Molinuevo JL, Brosseron F, Traschütz A, Heneka MT, Struyfs H, Engelborghs S, Sleegers K, Van Broeckhoven C, Zetterberg H, Nellgård B, Blennow K, Crispin A, Ewers M, Haass C

doi: 10.15252/emmm.201506123 http://embomolmed.embopress.org/content/early/2016/03/03/emmm.201506123

EMBO

Related Cognitive Impairment Articles:

Genomic copy number variants contribute to cognitive impairment in the UK
Genetic alterations of rare deletions or duplications of small DNA segments, called copy number variants (CNVs), have been known to increase risk of neurodevelopmental disorders such as schizophrenia, autism spectrum disorder, and intellectual disability.
Mild cognitive impairment (MCI)
Greek researchers demonstrated the potential of a self-administered virtual supermarket cognitive training game for remotely detecting mild cognitive impairment (MCI), without the need for an examiner, among a sample of older adults.
Link between sleep and cognitive impairment in the elderly
Daytime sleepiness is very common in the elderly with prevalence rates of up to 50 percent.
New guidelines could help improve research into vascular cognitive impairment
New guidelines have been developed that it is hoped will help to progress research into vascular cognitive impairment following a study led by academics at the University of Bristol that brought together the views of over 150 researchers in 27 countries.
Depression prevalence in patients with mild cognitive impairment
Depression commonly occurs in patients with mild cognitive impairment and a new review of the medical literature suggests an overall pooled prevalence of 32 percent, according to an article published online by JAMA Psychiatry.
Research provides insights on the link between kidney damage and cognitive impairment
Kidney damage was linked with worse performance on tests of global cognitive function, executive function, memory, and attention.
Mild cognitive impairment patients take about 3 medications for concomittant diseases
Dr. Vasileios Papaliagkas, the corresponding author of the paper, pointed that the vast majority of MCI patients were taking at least one medication, whereas slightly less than half of the patients (40 percent) took at least four medications.
Post-mortem assessment guidelines for vascular cognitive impairment
New research, led by academics at the University of Bristol, has outlined the first validated set of pathological criteria for assessing the likelihood that cognitive impairment was caused by vascular disease.
Study: Training helps those with mild cognitive impairment
New research from the Center for BrainHealth at the University of Texas at Dallas shows that strategy-based reasoning training can improve the cognitive performance for those with mild cognitive impairment, a preclinical stage of those at risk for Alzheimer's disease.
Why are blacks at higher risk for cognitive impairment?
Social and economic disadvantages play a significant role in why blacks face a much higher risk than whites of developing cognitive impairment later in life, indicates a national study led by a Michigan State University sociologist.

Related Cognitive Impairment Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Bias And Perception
How does bias distort our thinking, our listening, our beliefs... and even our search results? How can we fight it? This hour, TED speakers explore ideas about the unconscious biases that shape us. Guests include writer and broadcaster Yassmin Abdel-Magied, climatologist J. Marshall Shepherd, journalist Andreas Ekström, and experimental psychologist Tony Salvador.
Now Playing: Science for the People

#514 Arctic Energy (Rebroadcast)
This week we're looking at how alternative energy works in the arctic. We speak to Louie Azzolini and Linda Todd from the Arctic Energy Alliance, a non-profit helping communities reduce their energy usage and transition to more affordable and sustainable forms of energy. And the lessons they're learning along the way can help those of us further south.