AD/PD 2026 highlights: Advancing early detection, diagnostics and therapeutics across neurodegenerative diseases

Novel immunotherapy approaches in Alzheimer’s disease

Early-phase clinical data of for IBC-Ab002, presented by Prof. Catherine Mummery (UCL Dementia Research Centre, UCL, London, UK), showed the anti-programmed death ligand 1 (PD-L1) monoclonal antibody, introduced a novel immune checkpoint-based approach to AD. In a Phase Ib randomized, double-blind, placebo-controlled study in patients with early AD (n=40), the therapy demonstrated a favourable safety and tolerability profile, with no serious adverse events or amyloid-related imaging abnormalities reported.¹

Exploratory cerebrospinal fluid biomarker analyses at 12 months suggested directionally favourable changes in markers associated with synaptic and neuronal integrity, including neurogranin, total tau and phosphorylated tau.¹

These findings support the proposed mechanism of action, whereby modulation of the peripheral immune system may promote neurorepair and reduce neuroinflammation.

Disease-modifying potential in dementia with Lewy bodies

Neflamapimod, an oral small-molecule therapy targeting neuroinflammatory pathways, demonstrated statistically significant and clinically meaningful effects on disease progression in patients with dementia with Lewy bodies (DLB) without Alzheimer’s co-pathology in the Phase IIb RewinD-LB trial.²

These findings, presented by Prof. John-Paul Taylor (Newcastle University, Newcastle, UK) are particularly notable given the absence of approved disease-modifying therapies for DLB. The results have informed the design of a registrational Phase III trial, planned to commence in the second half of 2026 following regulatory alignment.²

In addition, the inclusion of neflamapimod in the EXPERTS-ALS platform trial reflects growing interest in targeting shared neurodegenerative pathways across disease indications.

AI and longitudinal biology: Redefining Parkinson’s disease

The Chronos-PD programme highlighted the transformative potential of integrating AI, advanced proteomics and real-world longitudinal data to map the molecular trajectory of PD.³

Proof-of-concept findings presented by investigators demonstrated that biological changes associated with PD may be detectable up to 12 years prior to clinical diagnosis.³ The platform identified both established and novel biomarkers, including modulation of the CXCL12–cell adhesion molecule–integrin axis, and enabled the identification of distinct disease subtypes.³

Advancing precision diagnostics: Imaging TDP-43 pathology

New data from a Phase I study of the positron emission tomography tracer ACI-19626 demonstrated the feasibility of in vivo imaging of TDP-43 pathology in humans.⁴

Initial findings showed higher tracer uptake in key brain regions in patients with genetically defined frontotemporal dementia compared with healthy controls, alongside favourable safety and pharmacokinetic profiles.⁴

Given the central role of TDP-43 pathology across multiple neurodegenerative diseases, including frontotemporal dementia and ALS, this approach may support the development of precision medicine strategies.

Targeting disease biology in multiple system atrophy

Emerging insights into the role of α-synuclein in multiple system atrophy (MSA) highlighted ongoing efforts to link pathophysiology with biomarker development and targeted therapies.⁵

Discussions emphasised the importance of early diagnosis, improved referral pathways and the development of biomarkers capable of identifying disease at earlier stages. In parallel, therapeutic strategies targeting α-synuclein aggregation continue to evolve.⁵

Translational progress in amyotrophic lateral sclerosis

Advances in ALS were highlighted by new data on PrimeC, a combination therapy comprising ciprofloxacin and celecoxib. Phase II clinical and biomarker data support its continued development, with progression towards a global Phase III programme.⁶

The therapeutic approach aims to modulate multiple disease pathways, including neuroinflammation and neuronal degeneration, reflecting the complex pathophysiology of ALS.

References

1. Mummery C. ImmunoBrain Phase Ib study of IBC-Ab002 in early Alzheimer’s disease. Presented at: Alzheimer’s and Parkinson’s Diseases Conference (AD/PD), Copenhagen, Denmark, 17–21 March 2026.
2. Taylor JP. CervoMed Phase IIb RewinD-LB trial of neflamapimod in dementia with Lewy bodies. Presented at: Alzheimer’s and Parkinson’s Diseases Conference (AD/PD), Copenhagen, Denmark, 17–21 March 2026.
3. Lehallier B. Chronos-PD: precise tracing of longitudinal molecular changes in preclinical and clinical phases of Parkinson’s disease. Presented at: Alzheimer’s and Parkinson’s Diseases Conference (AD/PD), Copenhagen, Denmark, 17–21 March 2026.
4. Seredenina T. Initial clinical characterization of [18F]ACI-19626: the first-in-class TDP-43 PET tracer. Presented at: Alzheimer’s and Parkinson’s Diseases Conference (AD/PD), Copenhagen, Denmark, 17–21 March 2026.
5. Cucca A. Oral D1/D2 agonist Lu AF28996: efficacy and tolerability in people with Parkinson’s disease with motor fluctuations with or without dyskinesia: open-label phase Ib results. Presented at: Alzheimer’s and Parkinson’s Diseases Conference (AD/PD), Copenhagen, Denmark, 17–21 March 2026.
6. Lunetta C. From PARADIGM to PARAGON: advancing PrimeC for ALS through clinical and biomarker insights towards a global Phase III trial. Presented at: Alzheimer’s and Parkinson’s Diseases Conference (AD/PD), Copenhagen, Denmark, 17–21 March 2026.