Researchers at the Karolinska Institute have identified astrocytes as a promising target for the early detection of Alzheimers disease due to their speedy action to its progression. In a research study released in Nature Reviews Neurology, they checked out the role of astrocytic α7nAChRs, a subunit of nicotinic acetylcholine receptors, in Alzheimers disease pathology and biomarkers. The researchers propose that targeting astrocytic α7nAChRs as an early biomarker with imaging PET-tracers could change Alzheimers illness medical diagnosis and restorative interventions. This discovery could lead to brand-new biomarkers for early medical diagnosis and brand-new targets for disease-modifying treatments, with potential implications for other neurodegenerative conditions including reactive astrogliosis.
Alzheimers illness is the most popular cause of dementia affecting millions of individuals worldwide. As the changes in brain function start around 10-20 years before the medical onset of Alzheimers disease, there is a strong interest in the recognition of early markers that can be predictive of future psychological health/cognitive decrease.
In this context, astrocytes are one of the promising targets due to their early and quick reaction to Alzheimers disease progression. Astrocytes represent essential homeostatic cells in the brain controlling a large selection of functions required for ideal brain operating and homeostasis. Most notably, they react to brain insults/injuries and disease states by a particular defense procedure, reactive astrogliosis.
In Alzheimers illness, the function of astrocytes is still uncertain. A number of recent studies reveal that reactive astrogliosis can precede other well-known pathological hallmarks of Alzheimers disease, such as amyloid deposition (Aβ) and tau tangles. It is hence important to define brand-new astrocytic biomarkers to deepen our understanding of reactive astrogliosis in the Alzheimers illness continuum.
In this context, the crosstalk between cholinergic signaling and reactive astrogliosis could hold the key to understanding the early reactions of glial cells to brain pathology and injury. The landmark Cholinergic Hypothesis of Alzheimers disease was proposed nearly 4 decades earlier, and led the way for the advancement of cholinesterase inhibitors– so far, the gold-standard therapy for Alzheimers disease.
Unique Astrocytic α7nAChRs biomarker as a bridge linking reactive astrogliosis, cholinergic and the amyloid waterfall hypotheses in Alzheimers disease pathogenesis. Credit: Igor Fontana
In this paper, the authors revisited the cholinergic signaling paths with the goal of exploring the last 20 years of research on astrocytic α7-subunit of the nicotinic acetylcholine receptors (α7nAChRs) to shed light on their role in the context of Alzheimers disease pathology and biomarkers. They discussed the likely participation of astrocytic α7nAChRs in the instigation and potentiation of early Aβ pathology and highlighted a number of new mechanistic paths of AD pathogenesis.
Based on these mechanistic pathways, the authors proposed that astrocytic α7nAChRs could be a crucial bridge connecting reactive astrogliosis, cholinergic, and the amyloid cascade hypotheses in Alzheimers illness (see the illustration listed below). Targeting astrocytic α7nAChRs as an unique early biomarker with different imaging PET-tracers (see their previous research study news 1. Inflammatory changes in the brain twenty years prior to Alzheimer onset 2. Possible new PET tracer for early detection of Alzheimers in this context) might be a game changer in the medical setting for future Alzheimers illness diagnostic and restorative interventions..
The researchers think this paper will open new avenues in regards to recognizing unique biomarkers for early diagnosis of Alzheimers illness and brand-new targets for disease-modifying treatments and will have broad medical implications, including other neurodegenerative disorders in which reactive astrogliosis is also observed. They have currently begun to put this brand-new hypothesis to the test with our unique in-house discovered and developed α7nAChRs PET-tracer KIn-83, which has actually been thoroughly characterized in postmortem human brains and soon will reach the very first in man PET studies.
Reference: “The role of astrocytic α7 nicotinic acetylcholine receptors in Alzheimer disease” by Igor C. Fontana, Amit Kumar and Agneta Nordberg, 28 March 2023, Nature Reviews Neurology.DOI: 10.1038/ s41582-023-00792-4.
Scientists at the Karolinska Institute have actually recognized astrocytes as an appealing target for the early detection of Alzheimers illness due to their quick reaction to its development. The researchers propose that targeting astrocytic α7nAChRs as an early biomarker with imaging PET-tracers might revolutionize Alzheimers disease diagnosis and therapeutic interventions. As the changes in brain function begin around 10-20 years before the scientific beginning of Alzheimers disease, there is a strong interest in the recognition of early markers that can be predictive of future psychological health/cognitive decline. In this context, astrocytes are one of the appealing targets due to their swift and early response to Alzheimers disease development. It is therefore vital to define new astrocytic biomarkers to deepen our understanding of reactive astrogliosis in the Alzheimers illness continuum.
