18F-AV1451 pet detects tau pathology in mapt mutation carriers and correlates strongly with immunohistochemistry of tau aggregates

Forskningsoutput: TidskriftsbidragPublicerat konferensabstract

Abstract

Background: The Tau PET ligand 18F-AV1451 has been shown to reliably detect paired helical filaments of tau in Alzheimer's disease, but it is not yet known whether it binds to the tau aggregates present in patients with mutations in the gene (MAPT) coding for the tau protein. Further, no study has yet compared the cerebral retention of 18F -AV1451 with the tau aggregates revealed using neuropathology. Methods: Three patients from a Swedish family carrying the R406W mutation of MAPT were assessed with cognitive tests and subjects underwent 18F-AV1451 and 18F-Flutemetamol PET scans. Further one of younger subjects also underwent an 18F-FDG PET scan. The oldest subject died two weeks after the scan and the brain was processed for neuropathology. Tau immunohistochemistry was performed on brain sections from affected and unaffected brain regions. Results: Two mutation carriers, aged 56 and 60 years, had disease durations of 5-10 years and still only exhibited mild-moderate episodic memory impairment and no clear behavioural deficits. The MRI revealed only slight cortical atrophy and 18F-AV1451 PET imaging showed uptake in the hippocampus and the temporal lobes, especially in the inferior and anterior parts (Fig 1A, B). The uptake of 18F - AV1451 correlated well with hypometabolism revealed with FGD PET in one of the subjects. The third case, 76 years, had a disease duration of ≥20 years and exhibited clear cognitive impairment, behavioural disturbances, mutism and dysphagia. The CT scan showed generalised cortical atrophy with a pronounced temporal lobe atrophy and 18F -AV1451 PET imaging revealed uptake in the temporal and frontal lobes, as well as in the basal ganglia (Fig 1 C). The regional uptake of 18F -AV1451 correlated strongly with the tau aggregates revealed using immunohistochemistry (R2 = 0.80, P <0.01; Fig 2). All cases exhibited negative amyloid (18F -flutemetamol) PET scans. Conclusions: The in vivo uptake of 18F-AV1451 reflects the regional amount of tau aggregates revealed by neuropathological examination. Further, tau pathology in MAPT mutation carriers is accurately detected with 18F -AV1451 PET, which consequently can be used to track the effects of anti-tau therapies in this patient group. (Figure Presented) .

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi

Nyckelord

Originalspråkengelska
Sidor (från-till)723-724
TidskriftAlzheimer's and Dementia
Volym12
Utgivningsnummer7 Suppl
StatusPublished - 2016 jul 1
PublikationskategoriForskning
Peer review utfördJa
EvenemangAlzheimer’s Association International Conference 2016 - Metro Toronto Convention Centre, Toronto, Kanada
Varaktighet: 2016 jul 222016 jul 28
https://www.alz.org/aaic/about/overview.asp