A possible explanation has been found in a study for why apoE4, the most significant genetic risk factor associated with Alzheimer’s disease, fails to protect the brain from inflammation.
Alzheimer’s disease is characterised by the accumulation of plaques of the amyloid-β protein, chronic inflammation and impaired neuronal function in the brain. The most significant genetic risk factor for the disease is apoE4, a variant of apolipoprotein E, which is known for, among other things, advancing the onset of the disease. While more than half of all individuals with Alzheimer’s disease carry this variant, the exact effect of apoE4 on the development of the disease has remained unknown.
A study identified a more accurate link between the apoE4 gene and the part of the human body’s immune system that underlies, among other things, Alzheimer’s disease. This is known as the complement system, and it contributes to the destruction of foreign cells and easily triggers inflammatory responses in the body.
“We found that apoE4 poorly binds factor H, a regulatory factor of immunity. The factor H molecule is crucial in preventing complement-mediated inflammation”, says the principal investigator of the study.
“Usually, apoE binds factor H to the amyloid-β aggregates in the brain, thus reducing local inflammation. But apoE4 does not” the author points out. This results in the accumulation of harmful amyloid-β aggregates and inflammation in the brain.
According to the author, binding factor H to apoE4 could present a potential solution to preventing changes in the brain that lead to the onset of Alzheimer’s disease. Further research will soon be conducted to look for such a bridging molecule.
The amyloid-β aggregates associated with Alzheimer’s disease begin to form in the brain decades before the diagnosis of the memory disorder. Since the mechanism underlying these changes has not been sufficiently well known, drug development has focused on stopping or slowing down changes that have already taken place.
“The drugs currently in use do not prevent the onset of the disease itself,” the author confirms.
Alzheimer’s disease is a slowly progressing memory disorder with more than 10 million new cases every year. As the population ages, the number of patients with the disease will rise considerably. In the future, Alzheimer’s disease will increase human suffering, as well as the burden on public health and the economy.
“Determining the molecular mechanisms that affect the onset of Alzheimer’s disease is important for developing curative drugs and therapies in the future.”
The study, published in the EMBO Reports journal, was carried out both by using experimental cell culture models and investigating brain biopsy samples from patients with idiopathic normal pressure hydrocephalus (iNPH) syndrome.
https://www.embopress.org/doi/full/10.15252/embr.202256467
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Freduced-binding-of&filter=22
How apoE4 and complement factor contribute to neuroinflammation
- 1,007 views
- Added
Edited
Latest News
Protein that helps COVID-19…
By newseditor
Posted 26 Jul
Spinal Muscular Atrophy (SM…
By newseditor
Posted 26 Jul
Link between bowel movement…
By newseditor
Posted 26 Jul
Inhibition of IL-11 signall…
By newseditor
Posted 25 Jul
Brain changes linked to obe…
By newseditor
Posted 25 Jul
Other Top Stories
Alternate splicing sequence determinants identified!
Read more
MicroRNAs regulating cholesterol and triglyceride homeostasis ident…
Read more
RNA Controls Poly-glutamine Protein Phase Transitions
Read more
Nuclear membrane repairs the 'dark matter' of DNA
Read more
Transmembrane protein sorting driven by membrane curvature
Read more
Protocols
A systems biology approach…
By newseditor
Posted 24 Jul
quantms: a cloud-based pipe…
By newseditor
Posted 22 Jul
Emerging tools and best pra…
By newseditor
Posted 19 Jul
Directly selecting cell-typ…
By newseditor
Posted 17 Jul
PUFFFIN: an ultra-bright, c…
By newseditor
Posted 16 Jul
Publications
Hepatocyte-intrinsic SMN de…
By newseditor
Posted 26 Jul
Aberrant bowel movement fre…
By newseditor
Posted 26 Jul
A pseudoautosomal glycosyla…
By newseditor
Posted 26 Jul
Microglia protect against a…
By newseditor
Posted 26 Jul
Rigor and reproducibility i…
By newseditor
Posted 26 Jul
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar