Abstract
AbstractBackgroundIncreasing evidence suggests that degeneration of Locus Coeruleus (LC) neurons is a common feature of various neurodegenerative diseases. Including patients neuropathologically diagnosed with frontotemporal lobar degeneration (FTLD). Based on the histopathological patterns FTLD has been categorized into three distinct subtypes; FTLD with tau immunoreactivity inclusion (FTLD‐tau), FTLD with TDP‐43 (transactive response DNA‐binding protein 43 kDa) immunoreactivity inclusion (FTLD‐TDP), and FTLD with other than tau and TDP‐43 immunoreactivity inclusion (FTLD‐Others). However, the significance of LC degeneration as a marker of the FTLD subtypes has not been fully explored. The purpose of this study was to investigate if the graded LC hypopigmentation can be used as a biomarker to separate distinct subtypes of FTLD.MethodThe sample included 63 participants from the National Alzheimer’s Coordinating Center’s (NACC) data sets who had ante mortem neuropathological and CSF data. LC pigmentation was graded as 0 = none, 1 = mild, 2 = moderate, and 3 = severe. The relationship between LC gross anatomy (hypopigmentation) and CSF A‐beta and Tau levels was explored. Also, the relationship between LC hypopigmentation and FTLD type was investigated. Moreover, markers of cerebrovascular diseases, including infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy, were investigated for their correlation with LC hypopigmentation.ResultThe hypopigmentation of LC is highly correlated with FTLD‐tau, then with a lower degree with FTLD‐TDP and less correlated with FTLD‐Other. Both LC and Substantia Nigra damage was correlated with CSF tau. We did not find statistically significant correlations between FTLD and cerebrovascular disease markers.ConclusionAnte mortem LC hypopigmentation could be used as a biomarker to differentiate underlying FTLD‐tauopathies from clinically similar FTLD‐TDP proteinopathies.
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