Retiring the term FTDP-17 as MAPT mutations are genetic forms of sporadic frontotemporal tauopathies

Abstract

See Josephs (doi:) for a scientific commentary on this article.Mutations in the MAPT gene on chromosome 17 are associated with frontotemporal lobar degeneration (FTLD). Mutation-associated cases are currently classified separately from sporadic cases with tau inclusions, as FTDP-17, but Forrest et al. provide evidence that these cases should in fact be considered familial forms of FTLD-tau subtypes.

Are mutations in MAPT associated with GGT type III?

“…Globular glial tauopathy (GGT) is the most recently described pathological subtype of frontotemporal lobar degeneration with tau-immunopositive inclusions (FTLD-tau) [1]. It is a rare disorder with approximately 70 cases described in the literature and has been reported to occur as a concomitant pathology in elderly patients with Alzheimer's disease [2]. Further pathological subtypes (GGT Type I-III) are recognized based on the density and morphology of tau-immunopositive inclusions, and regional involvement of pathology [1].…”

“…Scale bars represent 100 lm in the grey and white matter images, and 20 lm for higher magnification images of globular astrocytic inclusions (GAI), globular oligodendroglial inclusions (GOI) and coiled bodies (CB). 1 GGT cases with a mutation in MAPT previously reported in[1,2] 2. Age at diagnosis and disease duration in GGT Type III cases (n = 7) are expressed as the median (range).…”

Adeno‐associated virus‐based Alzheimer's disease mouse models and potential new therapeutic avenues

“…These include apolipoprotein E4 ( APOE4 ) as the major genetic risk factor, as well as BDNF , TREM2 , and many others (see Ulrich, Ulland, Colonna, & Holtzman, ). Although no familial AD mutations have been identified in the Tau‐encoding microtubule associated protein Tau ( MAPT ) gene, pathogenic mutations in this locus have been found to underlie familial FTD with Tau pathology (Forrest et al, ). The identification of genetic mutations in familial AD and FTD paved the way for developing the first transgenic mouse models that reproduced the human neuropathology and resulted in progressive functional deficits (see Gotz & Ittner, ).…”

One decade ago, one decade ahead in progressive supranuclear palsy

“…Mutations in the gene encoding for tau ( MAPT ) have been associated with both PSP phenotypes and PSP pathology . However, MAPT mutations are not associated specifically with PSP, but can lead to any tau‐associated frontotemporal lobar degeneration (FTLD) subtype and its associated syndrome . Just before the association of FTLD with MAPT was recognized, a polymorphism in the MAPT gene was reported as a risk factor for PSP .…”

“…20 However, MAPT mutations are not associated specifically with PSP, but can lead to any tau-associated frontotemporal lobar degeneration (FTLD) subtype and its associated syndrome. 20,21 Just before the association of FTLD with MAPT was recognized, a polymorphism in the MAPT gene was reported as a risk factor for PSP. 22 Subsequent studies on this association led to the discovery of two haplotypes that influence the risk for sporadic PSP.…”