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Fig. 8 | Acta Neuropathologica Communications

Fig. 8

From: Distinct molecular patterns of TDP-43 pathology in Alzheimer’s disease: relationship with clinical phenotypes

Fig. 8

TDP-43 pathology presents distinct molecular patterns in ADTDP + CTF vs. ADTDP + FL and FTLD-TDP. TDP-43 lesions in AD cases consist of NCIs, NFT-like structures and few DNs, which are mostly positive for pTDP-43409 and pTDP-43409/410 presumably representing aggregates of N-terminal truncated pTDP-43409/410. Moreover, they were restricted to limbic regions, including the medial temporal lobe and amygdala. These cases comprised high amounts of pathological Aβ (plaques) and τ NFT pathology. On the other end of the spectrum, the TDP-43 proteinopathy in FTLD-TDP cases consist of a large abundance of DNs and NCIs, that were detected not only with pTDP-43 antibodies, but also C- and N-t-TDP-43 antibodies (C-t-TDP-43+ and N-t-TDP-43+, respectively). Moreover, these lesions were widespread in the brain. In addition, in these cases TDP-43 was phosphorylated in S403/404 residues, in addition to S409/S410. Similar to ADTDP + CTF cases, ADTDP + FL cases had high amounts of Aβ and p-τ. However, they comprised an FTLD-TDP-like molecular pattern, which mostly consisted of NCIs, DNs and NFT-like lesions that comprise the full-length protein with phosphorylation of S403/404 in addition to S409/410, and that are widespread in the brain. ADTDP- cases were clinically AD. ADTDP + CTF cases mostly presented a clinical AD phenotype, with some cases presenting svPPA or additional behavioral deficits. Most ADTDP + FL cases presented symptomatic AD, with some cases presenting additional behavioral or language problems and other cases presenting bvFTD. FTLD-TDP cases presented a clinical picture of FTD

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