Alzheimer's disease (AD) will soon become a public health crisis. There currently are no treatments that delay the onset or prevent the progression of AD, though several promising candidates are in development. It will, therefore, be important to have biomarkers that can identify individuals at high risk in order to target them for clinical trials, disease-modifying therapies and to monitor therapy. AD pathology (e.g., A(3 plaques) begins 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 CSF AP42 have been shown to be an excellent marker of cortical amyloid early in the disease, whereas CSF tau/AP42 and ptaui8i/AP42 ratios are useful in predicting future cognitive decline. It is unclear, however, how early in the disease process such changes in CSF become detectable, so efforts are being made to study younger cohorts in the hopes of identifying affected individuals at the very earliest stages. Our long term goal is to fully understand the longitudinal evolution of biomarker changes during the natural course of AD. Project 2 begins to address this goal.
Aim 1 : Obtain standardized measures of Ap4o, AP42, tau, ptaui8i, and novel markers YKL-40, and VILIP-1 in fasted CSF samples and APi^o, Apx-40, Api^2, and APx-42in matched, fasted plasma samples using enzymelinked immunosorbent assays (plate-based ELISA) and xMAP (Luminex, bead-based) technologies.
Aim 2 : In longitudinal studies, assess the annual rate of change in biomarker levels as a function of family history and APOE e4 status, and investigate whether low CSF AP42 levels, or a drop in AP42 over time, predict future change in other biomarker analytes, such as tau, ptauisi, neuroinflammatory markers (e.g.,YKL-40), or putative markers of neurodegeneration (e.g., VILIP-1).
Aim 3 : Correlate fluid biomarker measures (and rate of biomarker change over time) with future cognitive decline (Clinical Core), changes in cortical amyloid load as assessed by PIB (Project 1), neuropsychological measures (Project 3), and structural/functional neuroimaging measures (Project 4).
There are currently no effective treatments that will prevent Alzheimer's 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 would aid in disease diagnosis and prognosis and assessing disease risk. 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.
|Schindler, Suzanne E; Sutphen, Courtney L; Teunissen, Charlotte et al. (2018) Upward drift in cerebrospinal fluid amyloid ? 42 assay values for more than 10 years. Alzheimers Dement 14:62-70|
|Sato, Chihiro; Barthélemy, Nicolas R; Mawuenyega, Kwasi G et al. (2018) Tau Kinetics in Neurons and the Human Central Nervous System. Neuron 98:861-864|
|Millar, Peter R; Balota, David A; Bishara, Anthony J et al. (2018) Multinomial models reveal deficits of two distinct controlled retrieval processes in aging and very mild Alzheimer disease. Mem Cognit 46:1058-1075|
|Babulal, Ganesh M; Chen, Suzie; Williams, Monique M et al. (2018) Depression and Alzheimer's Disease Biomarkers Predict Driving Decline. J Alzheimers Dis 66:1213-1221|
|Vlassenko, Andrei G; Gordon, Brian A; Goyal, Manu S et al. (2018) Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease. Neurobiol Aging 67:95-98|
|Gangishetti, Umesh; Christina Howell, J; Perrin, Richard J et al. (2018) Non-beta-amyloid/tau cerebrospinal fluid markers inform staging and progression in Alzheimer's disease. Alzheimers Res Ther 10:98|
|Stout, Sarah H; Babulal, Ganesh M; Ma, Chunyu et al. (2018) Driving cessation over a 24-year period: Dementia severity and cerebrospinal fluid biomarkers. Alzheimers Dement 14:610-616|
|Roe, Catherine M; Babulal, Ganesh M; Stout, Sarah H et al. (2018) Using the A/T/N Framework to Examine Driving in Preclinical AD. Geriatrics (Basel) 3:|
|Day, Gregory S; Musiek, Erik S; Morris, John C (2018) Rapidly Progressive Dementia in the Outpatient Clinic: More Than Prions. Alzheimer Dis Assoc Disord 32:291-297|
|Chen, Jason A; Fears, Scott C; Jasinska, Anna J et al. (2018) Neurodegenerative disease biomarkers A?1-40, A?1-42, tau, and p-tau181 in the vervet monkey cerebrospinal fluid: Relation to normal aging, genetic influences, and cerebral amyloid angiopathy. Brain Behav 8:e00903|
Showing the most recent 10 out of 352 publications