Glial molecular signatures as a liquid biopsy marker in Alzheimer's disease diagnosis

Alzheimer's disease (AD) is a neurodegenerative condition that is characterized by the misfolding of Amyloid Precursor Protein, hyperphosphorylation of tau protein, and neuroinflammation. This leads to the formation of extracellular senile amyloid beta plaque and neurofibrillary tangles in neurons, leading to neuronal degeneration. AD is the biggest cause of dementia globally. Currently, no therapies are available for AD and early diagnosis of the disease is a challenge. The most common fluid biomarkers for AD are: p-tau181, p-tau231, p-tau217, Aβ42/Aβ40 ratio, Neurogranin (Ng), Alzheimer's-associated neuronal thread protein (AD7c-NTP). All these biomarkers are detected in Blood, CSF, Saliva, and Urine with the help of different assays, PET scan, and MRI Imaging. These biomarkers are of neuronal origin and indicate neuronal stress. Brain also contains glial cells along with the neurons, which interact with the neurons in health and disease conditions. These glial cells also release molecules in disease induced stress. These markers can be used for early and differential diagnosis of AD and other dementia conditions. Studies also show that these glia biomarkers are released decades before the actual neuron degeneration begins. In this review, we will discuss these glial cells biomarkers identified in liquid biopsy for AD detection and progression.