Degeneration of the locus coeruleus is a common feature of tauopathies and distinct from TDP-43 proteinopathies in the frontotemporal lobar degeneration spectrum

We examined 280 patients including FTLD-tau (n = 94), FTLD-TDP (n = 135), and two reference groups: clinical/pathological AD (n = 32) and healthy controls (HC,n = 19). Adjacent sections of pons tissue containing the LC were immunostained for phosphorylated TDP-43 (1D3-p409/410), hyperphosphorylated tau (PHF-1), and tyrosine hydroxylase (TH) to examine neuromelanin-containing noradrenergic neurons. Blinded to clinical and pathologic diagnoses, we semi-q uantitatively scored inclusions of tau and TDP-43 both inside LC neuronal somas and in surrounding neuropil. We also digitally measured the percent area occupied of neuromelanin inside of TH-positive LC neurons and in surrounding neuropil to calculate a ratio of extracellular-to-intracellular neurom elanin as an objective composite measure of neurodegeneration. We found that LC tau burden in FTLD-tau was greater than LC TDP-43 burden in FTLD-TDP (z = − 11.38,p <  0.0001). Digital measures of LC neurodegeneration in FTLD-tau were comparable to AD (z = − 1.84,p >  0.05) but greater than FTLD-TDP (z = − 3.85,p <  0.0001) and HC (z = − 4.12,p <  0.0001). Both tau burden and neurodegeneration were consistently elevated in the LC across pathologic and clinical subgroups of FTLD-tau compared to FTLD-TDP subgroups. Moreover, LC tau burden positively correlated with neurodegeneration in the total FTLD group (rho = 0.24,p = 0.001), while TDP-43 burden did not cor...

Source: Acta Neuropathologica - August 16, 2020 Category: Neurology Source Type: research