Tori Rodriguez, MA, LPC, AHC Publish DateJanuary 27, 202
At the 18th Annual Clinical Trials on Alzheimer’s Disease (CTAD) conference, held December 1 to 4, 2025, in San Diego, California, researchers presented new data spanning observational studies, biomarker analyses, and clinical development programs in Alzheimer disease (AD).
Key topics included emerging evidence on metabolic therapies such as GLP-1 agonists, advances in blood-based biomarkers for monitoring anti-amyloid treatment, continued development of subcutaneous lecanemab formulations, and persistent racial and ethnic disparities in biomarker-based clinical trial enrollment. Selected sessions on these topics are highlighted below.
Could GLP-1 Drugs Slow Cognitive Decline in AD?
Real-world findings from a retrospective longitudinal cohort study presented at CTAD 2025 suggested a potential link between glucagon-like peptide-1 (GLP-1) agonist use and a slower rate of cognitive decline in individuals with AD.1
Further research, including larger, more definitive studies, is warranted to confirm this potential neuroprotective effect [of GLP-1 agonists] and its underlying mechanisms.
Based on the emerging hypothesis that AD may involve metabolic dysfunction, the researchers explored whether metabolic-targeted therapies, specifically, GLP-1 agonists, could influence the progression of AD.1
Using de-identified electronic health record data from United States neurology practices, the researchers compared patients with AD who had a history of GLP-1 use with patients with AD and no history of GLP-1 use. The 2 cohorts were matched on key demographic characteristics and baseline cognitive assessment scores.1
Across analyses, the annualized rate of cognitive decline appeared slower among patients who received GLP-1 agonists compared with those who did not receive these medications. However, differences between cohorts did not consistently reach statistical significance.1
“This analysis underscores the value of using longitudinal real-world data to rapidly investigate novel therapeutic hypotheses,” the authors concluded.1 “Further research, including larger, more definitive studies, is warranted to confirm this potential neuroprotective effect [of GLP-1 agonists] and its underlying mechanisms.”
Link Between Plasma P-Tau217 and PET Amyloid Positivity
In a study of more than 100 patients enrolled in the University of California, San Francisco Alzheimer’s Infusion Clinic biobank, plasma phosphorylated tau 217 (p-tau217) levels were correlated with the degree of amyloid positivity on positron emission tomography (PET) at baseline and were found to decrease following treatment with lecanemab.2
The researchers aimed to assess whether plasma biomarkers could help predict treatment response and monitor amyloid-related imaging abnormalities (ARIA) in patients receiving disease-modifying therapies for AD, noting that blood-based approaches are more accessible and scalable than imaging modalities such as magnetic resonance imaging (MRI) or PET. While plasma p-tau217 has shown promise in phase 3 clinical trials, real-world evidence remains limited.2
Participants underwent biobanking at each infusion during the first 3 months of treatment, with subsequent sampling at least every 3 months thereafter. In addition to p-tau217, patients underwent repeated measurements of neurofilament light chain and glial fibrillary acidic protein. Most participants completed pre-treatment amyloid PET imaging at baseline, where available.2
Baseline p-tau217 levels were correlated with the degree of amyloid PET positivity, with a stronger correlation observed when patients with impaired renal function were excluded from the analysis (r =0.43). Reductions in p-tau217 were detectable by 24 weeks of lecanemab treatment, with an approximate 11% decrease, and continued thereafter.2
No significant changes in neurofilament light chain or glial fibrillary acidic protein were observed immediately prior to the development of ARIA, suggesting that these markers may not be useful for predicting ARIA onset in clinical practice.2
Plasma p-tau217 “may potentially track amyloid clearance in treatment clinics as soon as 24 weeks, although p-tau217 alone may not be sufficient for optimal monitoring of amyloid clearance in real-world populations,” the authors wrote.2 “Ongoing work is evaluating the performance of different p-tau217 assays with respect to variability in repeated measurements, response to treatment, and amyloid clearance by PET.”
Exploring Subcutaneous Lecanemab for AD Treatment Initiation
Several related studies presented at CTAD 2025 examined the safety, efficacy, pharmokinetics and usability of a subcutaneous autoinjector formulation of the humanized immunoglobulin G1 (IgG1) monoclonal antibody lecanemab in patients with early AD.3
Intravenous (IV) lecanemab is currently approved by the United States Food and Drug Administration (FDA) based on results of the phase 3 Clarity AD study, which demonstrated significant reductions in brain amyloid burden and a slowing in the rate of clinical decline in early AD.4
More recently, the FDA has approved a 360 mg maintenance dose of lecanemab, and the manufacturer is seeking FDA approval for a 500 mg subcutaneous dose for treatment initiation, with the goal of improving convenience, access, and safety for patients with AD.5,6 Researchers noted that subcutaneous lecanemab 500 mg is “being used as the backbone anti-amyloid therapy for the add on study of the anti-tau antibody etalanetug in early AD.”3
Data presented at CTAD demonstrated that weekly subcutaneous lecanemab 500 mg achieved bioequivalent exposure to biweekly intravenous lecanemab 10 mg/kg, with comparable effects on amyloid clearance, clinical efficacy, and rates of ARIA with edema or effusion (ARIA-E).3
In a separate analysis, subcutaneous lecanemab showed a safety and tolerability profile similar to that of IV administration, with lower rates of systemic injection reactions compared with infusion-related reactions observed with IV dosing.3
A human factors validation study involving 110 trained and untrained patients, caregivers, and clinicians found that the lecanemab autoinjector could be safely and effectively administered across user groups. Additionally, more than 96% of participants in a device acceptability study rated the autoinjector as very easy or extremely easy to use, with or without assistance.3
“The [subcutaneous] formulation of lecanemab may provide improved access, compliance, convenience, and patient safety (low rate of system injection reactions), and a diminished burden on patients, caregivers, and [health care professionals], with lower overall costs to healthcare systems,” the authors concluded.3
Racial and Ethnic Disparities with Biomarker-Based Trial Inclusion
An analysis of the Bio-Hermes study found that the use of biomarker-based diagnostic criteria for AD clinical trial enrollment may lead to disproportionate inclusion of White non-Hispanic patients compared with other racial and ethnic groups.7
Due to a shift from symptom-focused diagnosis to pathology-based diagnosis following the 2018 publication of the NIA-AA Research Framework: Towards a Biological Definition of Alzheimer’s Disease, clinical trials often confirm AD diagnosis using the AT(N) biomarker system. This approach relies on the detection of biomarkers related to amyloid beta pathology (A), tau pathology (T), and neurodegeneration (N) to determine a likely AD diagnosis.7
However, evidence from clinical trials suggests differential expression of amyloid and tau pathology across various racial and ethnic groups, despite similar clinical symptoms. These differences are associated with higher rates of screen failure and lower inclusion rates among non-White populations with the use of biomarker-based methods.7
In the present study, multiple analyses of data from the Bio-Hermes biomarker database showed that using a single cutoff for various biomarkers resulted in adequate representation of non-Hispanic White participants but underrepresentation of non-Hispanic Black and Hispanic participants. In one analysis, inclusion rates were 40.0% among non-Hispanic White participants compared with 21.1% among non-Hispanic Black participants and 35.9% among Hispanic participants.7
“Adjusting cutoffs for different racial and ethnic groups may provide a way to include subpopulations at similar rates,” the authors concluded.7 “More research is required to determine why different subpopulations exhibit different levels of biomarker expression and how those differences relate to symptoms of Alzheimer’s Disease.”
References:
- Gautieri D, Gagneja A, Dooley J. GLP-1 agonists and cognitive decline in Alzheimer’s disease: real-world evidence from the SITERX Alzheimer’s Real World Data Network. Abstract presented at: Clinical Trials on Alzheimer’s Disease (CTAD) 2025; December 1-4, 2025; San Diego, California. Abstract P298.
- Schwartz N, Ellingson T, Nguyen H, et al. Clinical utility of plasma biomarkers in anti-amyloid treatment clinic to evaluate treatment response and predict side effects. Abstract presented at: Clinical Trials on Alzheimer’s Disease (CTAD) 2025; December 1-4, 2025; San Diego, California. Abstract P275.
- Cohen S, Reyderman L, Irizarry M, et al. Lecanemab subcutaneous formulation for treatment initiation in early Alzheimer’s disease: optimizing patient care with a potential new option. Abstract presented at: Clinical Trials on Alzheimer’s Disease (CTAD) 2025; December 1-4, 2025; San Diego, California. Abstract LBS2.
- FDA converts novel Alzheimer’s disease treatment to traditional approval. News release. US Food and Drug Administration. July 6, 2023. Accessed January 19, 2026.
- FDA approves LEQEMBI® IQLIK™ (lecanemab-irmb) subcutaneous injection for maintenance dosing for the treatment of early Alzheimer’s disease. News release. PR Newswire. September 2, 2025. Accessed January 19, 2026.
- Eisai initiated rolling supplemental biologics license application to the U.S. FDA for LEQEMBI® IQLIK™ (lecanemab-irmb) as a subcutaneous starting dose for the treatment of early Alzheimer’s disease under fast track status. News release. Eisai Global. September 3, 2025. Accessed January 19, 2026.
Tori Rodriguez, MA, LPC, AHC, is an Atlanta-based journalist, licensed psychotherapist, and Ayurvedic health coach, creator of the body-positive wellness company Bettie Page Fitness, and author of 2 books – The Little Book of Bettie: Taking a Page from the Queen of Pinups and Bettie Page: The Lost Years. She holds a BS in psychology from Georgia State University and an MA in counseling psychology from the Georgia School of Professional Psychology. Tori has also managed a medical practice and was instrumental in developing Georgia’s multispecialty telemedicine program. Photograph courtesy of Brooklyn Brat Images.