TY  - JOUR
AU  - Courade, Jean-Philippe
AU  - Zetterberg, Henrik
AU  - Höglinger, Günter U
AU  - Dewachter, Ilse
TI  - The evolving landscape of Alzheimer's disease therapy: From Aβ to tau.
JO  - Cell
VL  - 188
IS  - 26
SN  - 0092-8674
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - DZNE-2025-01467
SP  - 7337 - 7354
PY  - 2025
AB  - A marked evolution in Alzheimer's disease (AD) therapy research is ongoing. In this perspective, we highlight emerging outcomes of tau-targeting approaches with disease-modifying potential evidenced by PET-based slowing of tau accumulation and early signs of cognitive benefit. We outline how decades of iterative amyloid β (Aβ)-trial refinement leading to the recent successes of approved anti-Aβ therapies have set the stage for accelerated optimization of next-generation trials. We summarize key learnings from first-generation tau immunotherapies and how these paved the way for early achievements in tau trials, while many challenges remain. Finally, we discuss the back-translation of clinical outcomes into fundamental insights on human tau pathobiology, and we outline challenges and future directions for AD therapy development including combination therapy and targets beyond Aβ/tau. Together, this provides a framework for next-generation AD and tau-therapy development toward increasingly efficient disease-halting interventions.
KW  - Alzheimer Disease: therapy
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: drug therapy
KW  - Alzheimer Disease: pathology
KW  - Humans
KW  - tau Proteins: metabolism
KW  - tau Proteins: antagonists & inhibitors
KW  - Amyloid beta-Peptides: metabolism
KW  - Amyloid beta-Peptides: antagonists & inhibitors
KW  - Immunotherapy: methods
KW  - Animals
KW  - Clinical Trials as Topic
KW  - A(I)TN (Other)
KW  - ASO (Other)
KW  - AT(X)N (Other)
KW  - ATN (Other)
KW  - Abeta therapy (Other)
KW  - Alzheimer's disease (Other)
KW  - PET imaging (Other)
KW  - amyloid (Other)
KW  - anti-sense oligonucleotides (Other)
KW  - clinical trial (Other)
KW  - immunization (Other)
KW  - inflammation (Other)
KW  - neurodegeneration (Other)
KW  - next-generation therapies (Other)
KW  - tau (Other)
KW  - tau therapy (Other)
KW  - tauopathies (Other)
KW  - therapy development (Other)
KW  - trial (Other)
KW  - tau Proteins (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41448139
DO  - DOI:10.1016/j.cell.2025.11.033
UR  - https://pub.dzne.de/record/283060
ER  -