A multi-center blinded prospective study of urine neural thread protein measurements in patients with suspected Alzheimer's disease.

OBJECTIVE: To investigate the utility of a clinical laboratory ELISA format assay that measures neural thread protein (NTP) in urine in the assessment of patients presenting with cognitive symptoms. DESIGN: A prospective blinded multicentered study. SETTING: Eight US specialty clinics for the evaluation of cognitive or memory disorder or dementia, including memory disorder and dementia clinics, neurology clinics, and psychiatry clinics, in 8 states. PARTICIPANTS: Prospectively enrolled consecutive patients who were newly referred to a specialty clinic for assessment of cognitive or memory disorder symptoms or dementia to rule out or rule in Alzheimer's disease (AD). MEASUREMENTS: Participants provided a first morning urine sample for UNTP measurement for testing at a central core laboratory and subsequently went through specialized diagnostic evaluations in accordance with established clinical criteria. Urine NTP measurement was compared to the diagnostic categorization of the patients as probable or possible AD (according to National Institute of Neurological Communicative Disorders and Stroke and the Alzheimer Disease and Related Disorders Association [NINCDS-ADRDA] criteria), mild cognitive impairment (MCI) (according to Quality Standards Subcommittee of the American Academy of Neurology [AAN] criteria) or definite non-AD. Clinical diagnoses were made without reference to UNTP measurement; the testing laboratory was blinded to both patient identity and clinical diagnoses. RESULTS: A total of 168 enrolled and consented patients provided qualifying urine samples and completed specialized diagnostic workups. There were 91.4% of subjects with probable AD, 37.7% of subjects categorized as possible AD, and 48.6% of subjects with MCI who had an elevated NTP measurement (>22 microg/mL). There were 90.7% of subjects diagnosed as definite non-AD who had a normal NTP measurement (< or =22 microg/mL). CONCLUSION: Noninvasive UNTP test results are potentially helpful as part of the workup of dementia for the nonspecialist to help in the decision as to whether referral and/or more detailed investigation is advisable.