CSF Biomarkers for Secondary Prevention Trials: Why Markers of Amyloid Deposition and Neurodegeneration Are Both Important.
Arch Neurol. 2012 Apr 23;
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The conclusion that elevated CSF p-tau levels with reduced Aβ levels (Aβ+/p-tau+) are better correlated with clinical decline in baseline CDR = 0 (cognitively normal) individuals will help the pharmaceutical industry/clinical researchers better stratify subjects in secondary prevention trials. For basic researchers, however, this study raises an interesting question. High CSF p-tau levels are considered to be indicative of neurodegeneration. So, what do 19 (out of 107) individuals with elevated p-tau levels but without amyloid pathology (Aβ-/p-tau+) with baseline CDR = 0 represent? The mean age of these individuals is 78 years, making them unlikely to represent frontotemporal dementia with parkinsonism (FTDP) (where mean age of onset is around 49) or other tauopathies. Also, this population remained CDR = 0 at the end of the three-year follow-up period, indicating the neurodegeneration, as indicated by high p-tau does not result in clinical deficits.