Nanoscience enables ultrasensitive detection of Alzheimer's biomarker

Alzheimer's disease (AD), which afflicts an estimated 16 million people worldwide, is a neurodegenerative dementia characterized by memory loss and cognitive impairment (1). Symptoms begin with mild cognitive impairment that cannot be distinguished from other more benign forms of age-related dementia. Even as the disease progresses, clinical diagnosis can be made with only 65–90% accuracy. AD cannot be definitively diagnosed until after death, when brain tissue can be examined for the senile plaques and neurofibrillary tangles characteristic of the disease (2). The plaques result from aggregation of amyloid-β peptides and were long thought to be responsible for AD pathogenesis; however, their presence does not always correlate with neurological symptoms. Smaller, soluble oligomers of these peptides, referred to as amyloid-β-derived diffusible ligands (ADDLs), have recently been hypothesized as the causative agent in AD-related memory loss (3). Support for the role of ADDLs comes from their neurotoxicity (4), presence at elevated levels in the brains of AD patients as compared with age-matched controls (5), and mouse studies that indicate a reversal of memory loss upon injection of amyloid-β antibodies (6, 7). The work of Klein, Mirkin, and coworkers in this issue of PNAS (8) takes a significant step forward by demonstrating elevated ADDL concentrations in the cerebrospinal fluid (CSF) of patients who had been diagnosed (postmortem) with AD, as compared with healthy subjects. The correlation of CSF ADDL levels with disease state offers promise for …