Authors: Alice Weatherston
Within Alzheimer’s disease, microglia have been found to become impaired, resulting in an inability to clear the brain of foreign structures such as beta-amyloid peptides. New research however has focused on the possibility of prompting macrophages to take over the role of dysfunctional microglia, highlighting a potential new mechanism for immune action against the disease. The research was carried out at Charité – Universitätsmedizin Berlin (Germany) and was published recently in The Journal of Experimental Medicine.
The team, led by Frank Heppner (Charité – Universitätsmedizin Berlin) aimed to decipher whether microglia could be driven to migrate to the brain in a mouse model of Alzheimer’s with ablated microglia.
The ablation of the microglia resulted in an emergency infiltration response in which blood-borne macrophages migrated from peripheral sites to repopulate the brain. Following their migration, the peripheral macrophages developed further within the brain into bodies somewhat similar to microglia, however the cells did not show any evidence of clustering around Aβ deposits and had no impact on Azheimer’s pathology.
Heppner further explained the investigation: “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 clinical trials, and remains the subject of intense discussion.”
The Aβ vaccine however did not result in the macrophages becoming any more effective than the resident microglia, highlighting the need for further research into an effective stimulus for peripheral macrophages within an Alzheimer’s Disease brain.
Despite this Heppner is hopeful that the work is of significance within the field: “our data is of relevance, insofar as many recent studies have identified microglia as a crucial player in both the development and progression of Alzheimer’s disease. It is therefore of fundamental importance, not least in relation to the development of new treatment options, that we should gain a detailed insight into both the role and function of microglia and macrophages in AD.”
The team now hope to investigate the stimuli that will finally be able to restore the functioning of phagocytic cells within Alzheimer’s.