Patients with Alzheimer's disease have increased cellular amyloid uptake

Amyloid plaques are the main signature of Alzheimers disease (AD). Beta-amyloid (A{beta}) concentration in cerebrospinal fluid (CSF-A{beta}) and the density of amyloid depositions have a strong negative correlation. However, AD patients have lower CSF-A{beta} levels compared to cognitively normal people even after accounting for this correlation. The goal of this study was to infer variations of parameters in A{beta} metabolism of AD patients that underlie this difference using data from the Alzheimers Disease Neuroimaging Initiative cohort. We found that AD patients had dramatically increased rates of cellular amyloid uptake compared to individuals with normal cognition (NC). A group with late-onset mild cognitive impairment (LMCI) also exhibited stronger amyloid uptake, however this was less pronounced than in the AD group. Estimated parameters in the early-onset MCI group did not differ significantly from those in the NC group. A{beta} cytotoxicity depends on both the amount of peptide internalized by cells and its intracellular degradation into toxic products. Based on our results, we speculate that AD and LMCI are associated with increased cellular amyloid uptake which leads to faster disease progression, whereas the early-onset MCI may be mediated by the increased production of toxic amyloid metabolites.