Mapping out biomarkers for Alzheimer disease.
JAMA. 2011 Jan 19;305(3):304-5.
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The Yaffe paper is indeed very interesting. Finding a diagnostic and/or prognostic plasma biomarker is the real Holy Grail. It's still unclear, however, what alterations in plasma Aβ levels/ratios reflect. Dr. Zetterberg mentioned in the accompanying article that it would be great if we knew whether there was a relationship between plasma Aβ levels and PIB retention in the brain. Our own work in this area (Fagan et al., 2009; Figure 3) has demonstrated no relationship between plasma Aβ (Aβ1-40, Aβx-40, Aβ1-42, Aβx-42) levels and mean cortical PIB binding potential in a large cohort (n = 189) of cognitively normal individuals despite a strong relationship between PIB binding and CSF Aβ42 in this same cohort (as we and now several other groups have shown). Thus, the plasma Aβ story remains elusive...and warranting ongoing study.
Fagan AM, Mintun MA, Shah AR, Aldea P, Roe CM, Mach RH, Marcus D, Morris JC, Holtzman DM.
Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer's disease.
EMBO Mol Med. 2009 Nov;1(8-9):371-80.