Aβ deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer's disease

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The links between β-amyloid (Aβ) and tau in Alzheimer's disease are unclear. Cognitively unimpaired persons with signs of Aβ pathology had increased cerebrospinal fluid (CSF) phosphorylated tau (P-tau181 and P-tau217) and total-tau (T-tau), which increased over time, despite no detection of insoluble tau aggregates [normal Tau positron emission tomography (PET)]. CSF P-tau and T-tau started to increase before the threshold for Amyloid PET positivity, while Tau PET started to increase after Amyloid PET positivity. Effects of Amyloid PET on Tau PET were mediated by CSF P-tau, and high CSF P-tau predicted increased Tau PET rates. Individuals with MAPT mutations and signs of tau deposition (but without Aβ pathology) had normal CSF P-tau levels. In 5xFAD mice, CSF tau increased when Aβ aggregation started. These results show that Aβ pathology may induce changes in soluble tau release and phosphorylation, which is followed by tau aggregation several years later in humans.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
  • VU University Medical Center
  • Sahlgrenska University Hospital
  • University College London
  • Göteborgs universitet
  • University of California, San Francisco
  • Lilly Research Laboratories
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurovetenskaper
Originalspråkengelska
Artikelnummereaaz2387
TidskriftScience Advances
Volym6
Utgåva nummer16
StatusPublished - 2020
PublikationskategoriForskning
Peer review utfördJa