BChE inhibition can restore cholinergic signaling and may limit amyloid aggregation, while Nrf2 activation strengthens antioxidant defenses, suppresses neuroinflammation and protects against ferroptosis. Simultaneous modulation of these pathways is therefore expected to provide broader neuroprotection than single-target approaches and may better address the multifactorial nature of AD.
The NIH Accelerating Medicines Partnership Program for Alzheimer’s disease (AD) has named tyrosyl-tRNA synthetase (TyrRS, YARS1) as a therapeutic target in AD. Functional Longevity Labs Inc. has developed FLL-001, a potential first-in-class small-molecule TyrRS modulator designed to restore TyrRS levels and rescue its triad in post-mitotic neurons for the treatment of AD.
Pathological tau accumulation is a key driver of neurodegeneration in Alzheimer’s disease (AD) and other tauopathies such as progressive supranuclear palsy. Researchers at Alnylam Pharmaceuticals and Regeneron Pharmaceuticals Inc. presented preclinical efficacy data on ALN-5288 in tauopathy models.
Reduced endocannabinoid signaling has been linked to neuronal hyperexcitability in Alzheimer’s disease (AD), suggesting that dual inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) may restore endocannabinoid tone and alleviate hyperexcitability-driven symptoms, including agitation, a common neuropsychiatric manifestation of AD.
Pyroglutamate-modified amyloid-β (pE3-Aβ) is a highly pathogenic Aβ species that accumulates within amyloid plaques and contributes to aggregation, neuroinflammation and neuronal dysfunction in Alzheimer’s disease (AD). Researchers from Sound Biologics (Qilu Puget Sound Biotherapeutic Corp.) described the preclinical profile of PSB-229, a novel brain-shuttled anti-pE3-Aβ antibody in models of AD.
At the Alzheimer’s Association International Conference, researchers from Voyager Therapeutics Inc. presented preclinical efficacy data for VY-1706, a blood-brain barrier-penetrant AAV9 gene therapy designed to reduce tau levels in models of Alzheimer’s disease (AD).
Tuesday brought what was arguably the most anticipated presentation of the 2026 Alzheimer’s Association International Conference when Catherine Mummery, head of novel therapeutics at University College London’s Dementia Research Center, presented data from the phase II Celia trial of tau-lowering antisense oligonucleotide diranersen (BIIB-080, Biogen Inc.). Based on both clinical and biomarker data, “Celia establishes a proof of concept,” Mummery said, that reducing tau may slow the progression of Alzheimer’s disease.
The U.K. is setting up a nationwide registry of people with dementia, who will be pre-screened and consented, to speed up recruitment to clinical trials and collect real-world evidence of effectiveness once therapies are approved.
The Alzheimer’s Association International Conference (AAIC) is the world’s biggest dementia conference. And at the AAIC 2026 meeting, there is big buzz around tau. Sunday’s plenary speaker Ryan Watts, CEO of Denali Therapeutics Inc., highlighted tau-lowering agents as being among the most exciting themes of the conference. “At this conference, we’re going to see additional clinical data that may validate [tau as] a second target in Alzheimer’s disease, amyloid being the first,” he told the audience.
