Worldwide, more than 20% of persons over the age of 85 suffer from Alzheimer’s disease. Deposits of beta-amyloid (Aβ) peptide represent an important target for research into Alzheimer’s disease. These peptide fragments, which accumulate in the brains of Alzheimer’s patients, play an important role in the pathogenesis of the disease. Now, a study from researchers at Universitätsmedizin Berlin was able to directly assess the ability of peripheral macrophages to reduce Aβ plaque pathology, with the newly recruited peripheral myeloid cells failing to cluster around Aβ deposits even with additional anti-Aβ antibody treatment. The team state that this is another step towards controlling the brain’s own immune system to counteract the effects of Alzheimer’s disease.
Previous studies suggest that, although central nervous system–resident microglia are believed to be ineffective at phagocytosing and clearing amyloid-β (Aβ), peripheral myeloid cells may constitute a heterogeneous cell population with greater Aβ-clearing capabilities. These studies also identify the very same microglia as a crucial player in both the development and progression of Alzheimer’s disease.
Earlier studies from the lab have demonstrated that the brain’s immune cells, known as microglia, are impaired in the course of Alzheimer’s disease. Thus, microglia in Alzheimer’s are unable to fulfill their primary purpose, which is the elimination of foreign substances or abnormal structures such as pathological beta-amyloid peptides. In the current study, the group set out to investigate whether it might be possible to prompt macrophages, the peripheral counterparts of microglia that reside outside the brain and in the blood, to migrate to the brain, in order to take over role of the dysfunctional microglia.
The current study used mouse model of Alzheimer’s disease with the microglia removed. Results show that this created an emergency situation, which prompted the brain to initiate an infiltration response, and resulted in blood-borne macrophages migrating from peripheral sites to repopulate the brain. Data findings show that these peripheral derived cells subsequently underwent further development in the brain that rendered them similar to microglia, however, without impacting Alzheimer’s pathology and, rather than clustering around Aβ deposits , they completely ignored their presence.
The group explain that in order to make these peripheral macrophages interested in Aβ peptides, Alzheimer’s disease mice harboring blood-borne macrophages instead of resident microglia in the brain were given an Aβ vaccine, an approach that is currently being investigated in several other clinical trials, and remains the subject of intense discussion. However, the researchers conclude that even this additional stimulation did not render these peripheral macrophages any more effective than the brain’s resident microglia.
The team surmise that motivating resident microglia or peripheral macrophages to realize their full potential will require a different, or additional, stimulus. They go on to add that it is of fundamental importance to gain a detailed insight into both the role and function of microglia and macrophages in Alzheimer’s disease. For the future, the researchers are now planning to conduct further studies aimed at identifying the missing stimulus which they hope will return the phagocytic cells to their original function.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
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Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.