OO006 - PATHOLOGICAL HALLMARKS IN THE RETINA OF PATIENTS WITH FRONTOTEMPORAL LOBAR DEGENERATION (ID 1540)
- Jurre Den Haan (Netherlands)
- Anke Dijkstra (Netherlands)
- Tjado H.J. Morrema (Netherlands)
- Frederique J. Hart de Ruyter (Netherlands)
- Frank D. Verbraak (Netherlands)
- Johannes F. De Boer (Netherlands)
- Yolande A.L. Pijnenburg (Netherlands)
- Annemieke J.M. Rozemuller (Netherlands)
- Femke Bouwman (Netherlands)
- Jeroen J.M. Hoozemans (Netherlands)
Abstract
Aims
Frontotemporal lobar degeneration (FTLD) is a heterogeneous disease, with distinct underlying pathologies that include TDP-43, tau and FUS. Currently no in-vivo biomarkers are available to differentiate these subtypes. The retina, as an extension of the brain, could provide a source of such biomarkers. The aim of this study is to assess the presence of TDP-43 in the retina.
Methods
Post-mortem eyes were collected by the Netherlands Brain Bank from FTLD-TDP(n=4), FTLD–tau(n=4), FTLD-FUS(n=1), AD(n=4), and control donors(n=4). FTLD-TDP cases carried a C9orf72 repeat expansion(n=3) or progranulin mutation(n=1). Eyes were fixed in 4% PFA and dissected in 4 quadrants, embedded in paraffin and cut in 10 µm sections. Immunohistochemical stainings were performed for panTDP-43, phosphorylated TDP-43 (pTDP-43), p62, dipeptides (polyGR/GP/GA) and phosphorylated tau (AT8).
Results
P62 and pTDP-43 immunopositive inclusions are observed at the border of the inner and outer plexiform layer (IPL and OPL). PanTDP-43 shows a nuclear staining. Poly-GR/-GA inclusions are observed in the inner nuclear layer in FTLD-TDP cases. AT8 immunostaining was observed in IPL and/or OPL. p62, pTDP-43 and dipeptide pathology are present in the retina of patients with FTLD-TDP. No p62, pTDP-43 and dipeptide inclusions are present in the retinas of control cases or other FTLD subtypes. Inclusions positive for p62 and pTDP-43 are observed in AD cases.
Conclusions
Manifestations of TDP-43 and dipeptide pathology are present in the retina of patients with FTLD-TDP. With the advances in ocular imaging techniques these findings provide opportunities for a non-invasive retinal biomarker for TDP-43.
