Biomarkers of Alzheimer’s disease: Past, present and future clinical use

Alzheimer’s disease (AD) is an age-related neurodegenerative disease and the leading cause of dementia worldwide. AD is associated with several neuropathologic changes including the progressive accumulation of extracellular amyloid-β (Aβ) plaques, intracellular neurofibrillary tau tangles, neuroinflammation, cerebral small vessel disease and neurodegeneration, many of which are known to begin years before the onset of clinical symptoms. As such, there is a growing interest in developing biomarkers that can be used to detect these changes in the brains of at-risk individuals to facilitate earlier and more accurate diagnosis. This may allow for earlier intervention with disease-modifying therapies to slow the progression of irreversible neurodegeneration and improve quality of life. The current review seeks to provide a concise overview of the neuropathology and genetics underlying AD, and then summarize the most promising clinically available and experimental biomarkers of AD. These include structural neuroimaging, functional magnetic resonance imaging (fMRI), positron emission tomography (PET), cerebrospinal fluid (CSF), and blood-based assays. Multiple potential clinical uses for these biomarkers are then described, including screening at-risk populations for disease, aiding in differential diagnosis of dementia and mild cognitive impairment (MCI), monitoring the impact of lifestyle intervention and disease modifying therapies, identification and treatment of neuropsychiatric symptoms of dementia, and aiding in planning for end of life care. Finally, additional areas of future research are discussed, including replication of biomarker studies in more diverse patient cohorts, characterization of real-world clinical and psychological impacts of biomarker testing, as well as novel biomarkers currently under investigation.