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Case Reports
. 2020 Jun 29;8(1):94.
doi: 10.1186/s40478-020-00977-8.

de novo MAPT mutation G335A causes severe brain atrophy, 3R and 4R PHF-tau pathology and early onset frontotemporal dementia

Kunie Ando  1 , Lorenzo Ferlini  2 , Valérie Suain  3 , Zehra Yilmaz  3 , Salwa Mansour  3 , Isabelle Le Ber  4 , Cécile Bouchard  5 , Karelle Leroy  3 , Alexandra Durr  4 , Fabienne Clot  6 , Marie Sarazin  7 , Jean-Christophe Bier  2 , Jean-Pierre Brion  8
Affiliations
Case Reports

de novo MAPT mutation G335A causes severe brain atrophy, 3R and 4R PHF-tau pathology and early onset frontotemporal dementia

Kunie Ando et al. Acta Neuropathol Commun. .
No abstract available

Keywords: FTLD-tau; MAPT; Neurofibrillary tangles; Tau pathology.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
de novo mutation of MAPT-G335A led to severe brain atrophy with glial and neuronal tau pathology constituted of 3R and 4R tau. a Macroscopic pathology of FTLD-tau with MAPT-G335A mutation. The fixed left cerebral hemisphere showed a severe circumscribed atrophy of frontal lobe and anterior temporal lobe (with sparing of posterior superior gyrus). Motor and sensory gyri and occipital lobe were relatively spared. b Coronal sections of fixed brain. The frontal horn of the lateral ventricle was markedly dilated. c H&E reveals a ballooned neuron (right) and microvacuolation. d-e Immunostaining with AT8 (Thermo Scientific) (pS202/T205 tau) revealed numerous NFT in the pyramidal layer of the hippocampal CA1–2 sector (d). Occasionally there were astrocytic plaque-like appearance of tau-positive deposits in the striatum, thalamus and temporal cortex (e). f B19 (total tau)-positive astrocyte, reminiscent of tufted astrocytes were observed in the thalamus, frontal cortex and temporal cortex. g Coiled bodies (arrowhead) were immunolabelled by RD4 (clone 1E1/A6, Millipore) (4R tau). h Coiled bodies (arrowhead) were Gallyas positive. i-k Pyramidal neurons of the hippocampal CA2–3 sector immunostained for anti-tau B19 (i), RD4 (4R tau) (j) and Gallyas staining (k). Arrows show intraneuronal 4R tau positive globular and elongated inclusions (d, i-k). l-n NFT were immunostained with RD3 (clone 8E16/C11, Millipore, l) (3R tau) and RD4 (4R tau) (m). n Gallyas staining in CA2 sector shows a classical NFT (right) and Gallyas-positive intraneuronal threads (left). o-p Transmission electron microscopy showing a cytoplasmic aggregate of filaments in the frontal cortex. At higher magnification (p) of the inset in o, both straight filaments and PHF were observed. o 12,000x; p 30,000x. q Sarkosyl insoluble tau from the frontal cortex of the proband (MAPT-G335A) immunoblotted with PHF1, RD3, RD4 and total tau (A0024, Dako) antibodies. Sarkosyl insoluble tau is constituted of hyperphosphorylated 3R and 4R tau. Scale bars, 5 cm for a-b; 20 μm for c-n; 500 nm for o and 30 nm for p
See this image and copyright information in PMC

References

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