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O1‐01‐06: Longitudinal changes in cerebrospinal fluid biomarkers of Alzheimer's disease during middle‐age in cognitively normal individuals with a positive family history
Author(s) -
Sutphen Courtney L.,
Shah Aarti R.,
Amos Matthew,
Vlassenko Andrei G.,
Benzinger Tammie L.S.,
Holtzman David M.,
Morris John C.,
Fagan Anne M.
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.207
Subject(s) - biomarker , cerebrospinal fluid , cohort , dementia , disease , cognitive decline , medicine , family history , oncology , longitudinal study , pathology , physiology , psychology , biology , biochemistry
Background: Alzheimer’s disease (AD) pathology likely begins to accrue w10-20 years before any cognitive signs or symptoms; thus, it is imperative to identify individuals early in the disease process, while they are still cognitively normal (“preclinical” stage), so emerging disease-modifying therapies have the best chance to preserve normal brain function. Data from cross-sectional studies demonstrate decreases in cerebrospinal fluid (CSF) Ab42 and increases in CSF tau species in cognitively normal elders who go on to develop future cognitive decline.What remains unclear is how early in the preclinical period such alterations become detectable and how these biomarker profiles change over time.Methods: TheWashington University Adult Children Study (ACS) is a longitudinal clinical and biomarker study of cognitively normal (Clinical Dementia Rating of 0), middle-aged individuals (age 45-74) with positive or negative family history of AD that is designed to investigate the time course of AD pathologic biomarker changes during the preclinical period. Levels of CSFAb42, tau and ptau181 at baseline and follow-up (mean w3 years) were obtained by ELISA. Results: Analysis of longitudinal CSF samples in the ACS cohort demonstrates annual decreases in Ab42 in mid middle-age (age 55-64) and increases in tau in late middle-age (age 65-74) in individuals with a positive family history of AD. Comparison of these CSF changes with longitudinal amyloid imaging and brain volumetric measures within the same cohort will shed light on the possible time course of and relation between the various pathologic markers during the preclinical period. Conclusions: Biomarker evidence of AD pathologies can be detected in middle-age while individuals are still cognitively normal. Amyloid-related measures appear to be detectable first, followed by measures of tangles and/or neurodegeneration. Together these data will be informative for the design and evaluation of disease-modifying “prevention” trials currently being developed.