Astrocyte Biomarkers in Alzheimer’s Disease

The neurocentric view of AD is evolving and the contributions astrocytes make to the disease’s pathological processes are finally considered. AD pathology triggers astrocyte reactivity, which imaging and fluid biomarkers can measure in vivo. Astrocyte dysfunction in AD could contribute to [18F]FDG-PET hypometabolism. Astrocytes are promising targets for developing novel, specific fluid or imaging biomarkers for detecting preclinical AD. Pharmacologically targeting astrocytes may lead to developing an effective treatment for AD. Astrocytic contributions to Alzheimer’s disease (AD) progression were, until recently, largely overlooked. Astrocytes are integral to normal brain function and astrocyte reactivity is an early feature of AD, potentially providing a promising target for preclinical diagnosis and treatment. Several in vivo AD biomarkers already exist, but presently there is a paucity of specific and sensitive in vivo astrocyte biomarkers that can accurately measure preclinical AD. Measuring monoamine oxidase-B with neuroimaging and glial fibrillary acidic protein from bodily fluids are biomarkers that are currently available. Developing novel, more specific, and sensitive astrocyte biomarkers will make it possible to pharmaceutically target chemical pathways that preserve beneficial astrocytic functions in response to AD pathology. This review discusses astrocyte biomarkers in the context of AD. Astrocytic contributions to Alzheimer’s disease (AD) progression were, until recently, largely overlooked. Astrocytes are integral to normal brain function and astrocyte reactivity is an early feature of AD, potentially providing a promising target for preclinical diagnosis and treatment. Several in vivo AD biomarkers already exist, but presently there is a paucity of specific and sensitive in vivo astrocyte biomarkers that can accurately measure preclinical AD. Measuring monoamine oxidase-B with neuroimaging and glial fibrillary acidic protein from bodily fluids are biomarkers that are currently available. Developing novel, more specific, and sensitive astrocyte biomarkers will make it possible to pharmaceutically target chemical pathways that preserve beneficial astrocytic functions in response to AD pathology. This review discusses astrocyte biomarkers in the context of AD. carbon-11-labelled positron emission tomography radiotracer that binds to the imidazoline2-binding site, highly expressed in astrocytes. carbon-11-labelled positron emission tomography radiotracer that binds to monoamine oxidase-B, mainly expressed in reactive astrocytes. amyloid-β peptide usually constituted of 40 or 42 amino acids. soluble toxic amyloid-β species composed by amyloid monomers (ranging from 12 to 150 kDa). β-sheet-insoluble conformation of amyloid-β, a histopathological feature of AD. a hypothetical model put forward in 1992 by John Hardy and Gerald Higgins describing amyloid-β deposition as the causative agent in AD, which results in downstream NFTs formation, cell loss, vascular damage, and cognitive decline. a transmembrane protein expressed in many tissues and concentrated in the CNS, which is cleaved into amyloid-β monomers. a hypothetical framework postulating that astrocytes take up glucose, metabolise it through glycolysis, and then fuel neurons with lactate in response to neuronal activity. a highly selective ‘physiological sieve’ that divides the circulating blood from the brain, controlling the movement of ions and molecules between these two compartments. intermediate filament protein expressed mainly in astrocytes and overexpressed in reactive astrocytes. chemical transmitters released by astrocytes, including glutamate, d-serine, and ATP. a fluid-clearance pathway composed by periarterial and perivenous spaces, and the interposed brain parenchyma that allows for clearance and redistribution of exogenous or endogenous molecules. medical imaging technique that uses strong magnetic fields, electric gradients, or radio waves for acquiring anatomical and functional images. enzyme that degrades biogenic and dietary amines predominantly located in the outer mitochondrial membrane of astrocytes but also in serotoninergic neurons. intermediate filament protein expressed in developing astrocytes (not adults) and re-expressed in adult reactive astrocytes. insoluble twisted fibres primarily composed of hyperphosphorylated tau protein, a canonical histopathological feature of AD. medical imaging technique that uses molecular agents labelled with positron-emitting radioisotopes allowing the visualisation of biological processes in vivo. a microtubule-associated protein (MAP) responsible for maintaining and promoting cell microtubule stability. intermediate filament protein expressed mainly in astrocytes and upregulated in reactive astrocytes.