With the increasing approval of Alzheimer’s disease-modifying therapies and the emergence of more accessible diagnostic tools, the treatment landscape in Alzheimer’s disease (AD) is undergoing a transformation. At AAIC 2025, several pivotal studies and technological innovations were showcased that could reshape both the short- and long-term management of AD.
In this expert interview, Prof. George Grossberg (Saint Louis University School of Medicine, St Louis, MO, USA) shares his perspective on the most promising agents in development, as well as his reflections on key findings from Alzheimer’s Association International Conference (AAIC) 2025.
Several promising investigational therapies were discussed at AAIC 2025. First, monoclonal antibodies targeting tau are gaining momentum. While amyloid has long been the primary focus of disease-modifying efforts, tau pathology correlates more directly with clinical symptoms. Agents in this class are still in early- to mid-phase trials, but the results so far are encouraging.
A major development has been the advancement of weekly subcutaneous injections of lecanemab, the anti-amyloid monoclonal antibody already approved for early-stage AD. Weekly subcutaneous dosing is being developed as a more convenient alternative to intravenous infusion. This could significantly improve patient adherence and access to therapy.1
Another important innovation involves trontinemab, a monoclonal antibody utilizing a “brainshuttle” platform pioneered by Roche. This technology enables the use of low systemic doses of the monoclonal antibody but achieving high penetration of the blood-brain barrier. Resulting in rapid plaque clearance but with lower side effects, including reducing the risk of amyloid-related imaging abnormalities (ARIA).2
Promising early preclinical studies are exploring oral formulations of monoclonal antibodies, which would be revolutionary in terms of accessibility. These are not yet in human trials, but the prospect of oral anti-amyloid therapy is exciting.
Finally, studies are also underway looking at whether anti-amyloid monoclonals targeting A beta, when administered to at-risk individuals, can delay or even prevent the onset of mild cognitive impairment (MCI) due to AD.
Three presentations from AAIC 2025 stand out as particularly impactful:
1. The POINTER Study Results3
This two-year, randomized controlled trial confirmed that a multi-domain lifestyle intervention significantly improved cognition in older adults at risk of AD. The study tested a structured “Brain Health Recipe”, including:
- At least 150 minutes of exercise per week
- Adoption of the MIND diet (a hybrid of Mediterranean and DASH diets with reduced sodium)
- Cognitive training
- Social engagement
- Health self-management of modifiable risk factors such as hypertension, diabetes, dyslipidaemia, obesity, sleep disorders and mood symptoms.
This study reinforces the idea that lifestyle modifications are not merely preventative but can also be therapeutic in at-risk populations.
2. Guidelines for Blood-Based Biomarkers (BBMs) in Clinical Practice4
New clinical guidance was issued for the use of BBMs in AD diagnosis, coinciding with the commercial availability of the Lumipulse® plasma assay, which measures phosphorylated tau 217 (p-tau217) and amyloid-beta 42. The guidelines recommend using BBMs only after comprehensive clinical evaluation and assessment. A negative BBM result effectively rules out AD in 97% of cases, while positive results should be confirmed with cerebrospinal fluid (CSF) biomarkers or amyloid PET imaging.
3. Positive Phase 2 Results for Blarcamesine in Dementia with Lewy Bodies (DLB)5
Blarcamesine (ANAVEX®2-73), a muscarinic M1 and sigma-1 receptor agonist, showed a 50% reduction in cognitive decline on the AD Assessment Scale-Cognitive Subscale (ADAS-Cog-13) over 48 weeks in patients with DLB. The drug was also well tolerated. This is the first robust signal of efficacy for a pharmacological treatment targeting core symptoms in Lewy body dementia. If confirmed in Phase 3 trials, this could be a landmark development for a population with very limited treatment options.
Article Highlights
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- Subcutaneous and blood-brain-barrier penetrating monoclonal antibodies are advancing Alzheimer’s treatment.
- The POINTER study confirms lifestyle interventions improve cognition in at-risk older adults.
- Blood-based biomarkers are now clinically viable, with new diagnostic guidelines released at AAIC 2025.
- Blarcamesine demonstrated significant cognitive benefit in dementia with Lewy bodies.
This content has been developed independently by Touch Medical Media for touchNEUROLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Editor: Katey Gabrysch, Editorial Director.
Disclosures: This short article was prepared by touchNEUROLOGY in collaboration with George Grossberg. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchNEUROLOGY utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
George Grossberg is a consultant for Acadia, Alpha Cognition, Axsome Therapeutics, Biogen, BioXcel, Bristol Myers Squibb, Eisai, Karuna, Lilly, Lundbeck, Maplight Therapeutics, Otsuka, and Takeda; has received grant/research support from NIA, and is a speaker’s bureau participant with Otsuka.
Cite: George Grossberg. New Alzheimer’s disease therapies and biomarker-driven strategies: Key AAIC highlights. touchNEUROLOGY. 04 September 2025.
References:
- Eisai Co., Ltd. Lecanemab subcutaneous formulation shows similar exposure, lower ARIA compared to intravenous in Phase 1 study. 2025. Available at: www.eisai.com/news/2025/news202553.html (accessed 4 September 2025).
- Clinical Trials Arena. Roche reports promising Phase III Alzheimer’s data with brain shuttle antibody trontinemab. 2025. Available at: www.clinicaltrialsarena.com/news/roche-alzheimers-phase-iii-advance (accessed 4 September 2025).
- Alzheimer’s Association. U.S. POINTER: Study results. 2025. Available at: www.alz.org/us-pointer/study-results.asp
(accessed 4 September 2025). - Alzheimer’s Association. New clinical practice guideline released for blood-based biomarkers in Alzheimer’s disease. 2025. Available at: aaic.alz.org/releases-2025/clinical-practice-guideline-blood-based-biomarkers.asp (accessed 4 September 2025).
- Anavex Life Sciences. Anavex Life Sciences announces positive precision medicine results from up to 4 years of oral blarcamesine treatment. 2025. Available at: www.anavex.com/post/anavex-life-sciences-announces-positive-precision-medicine-results-from-up-to-4-years-of-oral-blarca (accessed 4 September 2025).
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