BOSTON – The same biomarkers that successfully discriminate frontotemporal dementia from Alzheimer’s disease don’t appear very helpful in differentiating patients with frontotemporal dementia from those with subjective memory problems.
Low cerebrospinal fluid levels of amyloid beta 42 (Abeta42) and high levels of tau are now seen as important diagnostic hallmarks for Alzheimer’s. The median levels of those biomarkers in patients with FTD are significantly different from what is measured in individuals with Alzheimer’s disease, but levels of those markers are too similar between FTD patients and those with subjective memory problems to be useful in differential diagnosis, Dr. Yolande Pijnenburg said at the Alzheimer’s Association International Conference 2013.
Michele G. Sullivan/IMNG Medical Media
Dr. Yolande Pijninburg
Even if there were a significant correlation, its clinical specificity might be doubtful at this point, said Dr. Pijnenburg of the VU University Medical Center, Amsterdam. "Frontotemporal dementia is so pathologically heterogeneous that it’s almost unthinkable that we would find one specific biomarker."
The findings of her new study were a bit of a disappointment, failing to confirm her earlier work (Clin. Chem. Lab. Med. 2011;49:353-66), which suggested that both tau and phosphorylated tau (P-tau) might be diagnostically useful.
She examined biomarker levels in a cohort of 363 patients recruited from the Amsterdam Dementia Cohort and an associated memory clinic. Of these, 121 had Alzheimer’s disease, 121 had FTD, and 121 had subjective memory complaints that were not pathologic.
The FTD group illustrated Dr. Pijnenburg’s comment about diverse pathology: 91 had behavioral variant FTD and 30 met the Gorno-Tempini criteria for semantic dementia (temporal variant FTD), but 30 also met clinical criteria for Alzheimer’s.
All subjects had cerebrospinal fluid drawn for Abeta42, tau, and P-tau levels. The groups were well matched for age (mean, 62 years). The mean disease duration was about 3 years. The mean Mini Mental State Examination score was 24 in the FTD group, 21 in the Alzheimer’s group, and 28 in the controls with memory complaints.
Abeta42 was lowest in the Alzheimer’s patients at a median of 488 pg/mL. This was significantly lower than the level in either the FTD patients (848 pg/mL) or the normal controls (935 pg/mL). But between the FTD and control groups, neither the median levels nor the ranges were significantly different. The diagnostic accuracy was 89% for discriminating FTD from Alzheimer’s and 57% for discriminating FTD from controls.
The picture was similar for total tau. The level was highest in Alzheimer’s patients (median, 662 pg/mL), followed by the FTD group (345 pg/mL) and the control group (245 pg/mL). But again, neither those levels nor their ranges were significantly different from each other. The diagnostic accuracy was 81% for discriminating FTD from Alzheimer’s and 69% for discriminating FTD from controls.
P-tau was similarly elevated in Alzheimer’s patients (median, 86 pg/mL) and nearly identical in both FTD (42 pg/mL) and controls (45 pg/mL). The diagnostic accuracy was 87% for discriminating FTD from Alzheimer’s and 53% for discriminating FTD from controls.
The tau/Abeta42 ratio had a diagnostic accuracy of 91% for discriminating FTD from Alzheimer’s and 72% for discriminating FTD from the controls.
Dr. Pijnenburg expressed some hope for biomarker utility in the future, despite the rather low accuracy levels for the FTD/control discrimination in this study. "There was very little relevance for measuring Abeta42 or P-tau, but total tau and the tau/Abeta42ratio both do have some diagnostic interest," she said.
During discussion, she addressed several questions concerning unexpectedly low tau levels in the FTD cohort. Patients with FTD have a more rapid disease progression and more brain atrophy than do Alzheimer’s patients. Tau is also directly related to neurodegeneration. So why, she was asked, was there not more tau in the cerebrospinal fluid?
"My thought is that it could be related to the focal nature of FTD," she said. "Alzheimer’s is more diffuse."
Dr. Pijnenburg had no financial disclosures.
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