We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Defective Lipoprotein Binding in the Brain Linked to Alzheimer's Disease Risk

By LabMedica International staff writers
Posted on 03 Aug 2016
Mutations in the TREM2 (Triggering receptor expressed on myeloid cells 2) gene, which encodes a protein expressed selectively by microglia in the brain, have been linked to disrupted binding of lipoproteins and are associated with the development of Alzheimer’s disease (AD). More...


Previous studies had shown that microglia - immune cells that remove pathogenic materials from the brain in a manner similar to that of microphages in the immune system - from individuals with TREM2 mutations had decreased ability to bind to lipoproteins in the brain's extracellular milieu.

To study this phenomenon further, investigators at the biotech company Genetech (South San Francisco, CA, USA) performed a large unbiased screen of an extracellular recombinant protein library representing 1,559 extracellular proteins and identified a set of lipoprotein particles and apolipoproteins as ligands of TREM2.

They reported in the July 20, 2016, issue of the journal Neuron that the TREM2 ligands included the apolipoproteins APOE and CLU (APOJ), which are risk genes for AD, and that their binding was impaired by TREM2 mutations that conferred AD risk. Binding of these ligands by TREM2 was abolished or reduced by disease-associated mutations.

Overexpression of wild-type TREM2 was sufficient to enhance uptake of LDL, CLU, and APOE in heterologous cells, whereas TREM2 disease variants were impaired in this activity. Amyloid-beta was found to be bound to lipoproteins, and this complex was efficiently taken up by microglia in a TREM2-dependent fashion. Uptake of Amyloid-beta-lipoprotein complexes was reduced in macrophages from human subjects carrying a TREM2 AD variant. In addition, the investigators provided evidence that, through its interaction with lipoproteins, TREM2 could facilitate Amyloid-beta uptake by microglia and human macrophages.

"I think we are only scratching the surface of what TREM2 does," said senior author Dr. Morgan Sheng, vice-president of neuroscience at Genentech. "Lipoproteins float around in the blood, and their purpose is to carry cholesterol or lipids from one cell to another - as we all know, too much LDL is associated with high cholesterol and increased risk of cardiovascular disease. Lipoproteins also exist in the brain, but less is understood about their role there. "

"Overall, these studies further point towards microglia as playing an important role in the pathogenesis of Alzheimer's disease," said Dr. Shen. "It was a surprise that amyloid-beta was much more efficiently engulfed when bound in a lipoprotein complex, rather than when amyloid-beta aggregates were free and naked."

Related Links:
Genetech



New
Gold Member
Quality Control Material
iPLEX Pro Exome QC Panel
3-Part Differential Hematology Analyzer
Swelab Alfa Plus Sampler
New
Clostridium Difficile Toxin A+B Combo Card Test
CerTest Clostridium Difficile Toxin A+B
New
Gold Member
Serological Pipets
INTEGRA Serological Pipets
Read the full article by registering today, it's FREE! It's Free!
Register now for FREE to LabMedica.com and get access to news and events that shape the world of Clinical Laboratory Medicine.
  • Free digital version edition of LabMedica International sent by email on regular basis
  • Free print version of LabMedica International magazine (available only outside USA and Canada).
  • Free and unlimited access to back issues of LabMedica International in digital format
  • Free LabMedica International Newsletter sent every week containing the latest news
  • Free breaking news sent via email
  • Free access to Events Calendar
  • Free access to LinkXpress new product services
  • REGISTRATION IS FREE AND EASY!
Click here to Register








DIASOURCE (A Biovendor Company)

Channels

Hematology

view channel
Image: CitoCBC is the world first cartridge-based CBC to be granted CLIA Waived status by FDA (Photo courtesy of CytoChip)

Disposable Cartridge-Based Test Delivers Rapid and Accurate CBC Results

Complete Blood Count (CBC) is one of the most commonly ordered lab tests, crucial for diagnosing diseases, monitoring therapies, and conducting routine health screenings. However, more than 90% of physician... Read more

Immunology

view channel
Image: The Volition Nu.Q nucleosome assay runs on the IDS i10 automated analyzer platform (Photo courtesy of VolitionRx)

Groundbreaking Lateral Flow Test Quantifies Nucleosomes in Whole Venous Blood in Minutes

Diagnosing immune disruptions quickly and accurately is crucial in conditions such as sepsis, where timely intervention is critical for patient survival. Traditional testing methods can be slow, expensive,... Read more

Pathology

view channel
Image: A real-time trial has shown that AI could speed cancer care (Photo courtesy of Campanella, et al., Nature Medicine)

AI Accurately Predicts Genetic Mutations from Routine Pathology Slides for Faster Cancer Care

Current cancer treatment decisions are often guided by genetic testing, which can be expensive, time-consuming, and not always available at leading hospitals. For patients with lung adenocarcinoma, a critical... Read more
Copyright © 2000-2025 Globetech Media. All rights reserved.