Journal
EMBO MOLECULAR MEDICINE
Volume 1, Issue 8-9, Pages 371-380Publisher
WILEY
DOI: 10.1002/emmm.200900048
Keywords
amyloid; biomarker; cerebrospinal fluid; Pittsburgh compound B; preclinical Alzheimer's disease
Categories
Funding
- National Institutes of Health [P50 AG05681, P01 AG03991, P01 AG026276, P30 NS057105]
- National Institute of Neurological Disorders and Stroke [P30 NS048056]
- National Center for Research Resources, NIH [UL1 RR024992]
- Dana Foundation
- Charles and Joanne Knight Alzheimer Research Initiative
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Alzheimer's disease (AD) pathology is estimated to develop many years before detectable cognitive decline. Fluid and imaging biomarkers may identify people in early symptomatic and even preclinical stages, possibly when potential treatments can best preserve cognitive function. We previously reported that cerebrospinal fluid (CSF) levels of amyloid-beta(42) (A beta(42)) serve as an excellent marker for brain amyloid as detected by the amyloid tracer, Pittsburgh compound B (PIB). Using data from 189 cognitively normal participants, we now report a positive linear relationship between CSF tau/ptau(181) (primary constituents of neurofibrillary tangles) with the amount of cortical amyloid. We observe a strong inverse relationship of cortical PIB binding with CSF A beta(42) but not for plasma Ab species. Some individuals have low CSF A beta(42) but no cortical PIB binding. Together, these data suggest that changes in brain A beta(42) metabolism and amyloid formation are early pathogenic events in AD, and that significant disruptions in CSF tau metabolism likely occur after A beta(42) initially aggregates and increases as amyloid accumulates. These findings have important implications for preclinical AD diagnosis and treatment.
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