Alzheimer’s disease (AD) will soon become a public health crisis. There are currently no effective treatments that will prevent the disease, halt its progression or delay its onset, although several therapeutic approaches are being developed and tested in clinical trials. Parallel efforts are being channeled into developing biomarkers that can identify individuals at high risk in order to target them for clinical trials of disease-modifying therapies and to monitor therapy. Together these combined endeavors have the potential to provide physicians the tools to effectively diagnose and treat the disease, preferably even before the onset of cognitive decline.
AD pathology (e.g., Ab plaques and neurofibrillary tangles) has been estimated to begin ~10-20 years before the onset of cognitive symptoms. Even the earliest clinical symptoms are accompanied by neuronal and synaptic dysfunction/death. Thus, it will be critical to identify individuals with “preclinical” AD, prior to marked clinical symptoms and neuron loss, so new therapies will have the best chance to preserve normal brain function. Low levels of Ab42 in the cerebrospinal fluid (CSF) have been shown to be an excellent marker of cortical amyloid early in the disease, whereas CSF tau/Ab42 and ptau181/Ab42 ratios are useful in predicting future cognitive decline. However, it is unclear how early in the disease process such changes in CSF become detectable. To this end, with our colleagues at the Knight Alzheimer’s Disease Research center (ADRC) at Washington University, we are studying research participants that span a wide age range (45-90 years of age) in the hopes of identifying affected individuals at the very earliest stages of the disease. Our long term goal is to fully understand the longitudinal evolution of biomarker changes during the natural course of AD (both in late-onset “sporadic” cases and early-onset cases due to disease-causing autosomal-dominant mutations) in order to aid in disease diagnosis and prognosis (especially in the preclinical stage) and to facilitate the development of disease-modifying therapies.