Age- and amyloid-β-dependent initiation of neurofibrillary tau tangles: an improved mouse model of Alzheimer's disease without mutations in <em>MAPT</em>

Authors

Sneha Desai, Elena Camporesi, Gunnar Brinkmalm, Argyro Alatza, Jack I Wood, Takshashila Tripathi, Sumi Bez, Nazar Stasyuk, Haady B Hajar, Takashi Saito, Takaomi C Saido, John Hardy, Damian M Cummings, Jörg Hanrieder, Frances A Edwards

Abstract

bioRxiv [Preprint]. 2024 Nov 4:2024.11.04.621900. doi: 10.1101/2024.11.04.621900.

ABSTRACT

Introducing heterozygous humanized tau to App^NL-F/NL-F knock-in mice results in the first mouse model of Alzheimer's disease in which age and amyloid-β pathology interact to initiate neurofibrillary tau tangle pathology, not dependent on mutations in MAPT. Gradual progression from amyloid-β to tau pathology in NLFTau^m/h mice opens possibilities for understanding processes precipitating clinical stages of Alzheimer's disease and development of translatable therapies to prevent the onset of tau pathology.

PMID:39574656 | PMC:PMC11580841 | DOI:10.1101/2024.11.04.621900

UK DRI Authors

Prof Sir John Hardy

Group Leader

Harnessing genetics to build a better understanding of dementia

Prof Sir John Hardy