From Amyloid to Precision Neurodegeneration
Adjutor Group | Scientific & Industry Perspective
Each year, World Alzheimer’s Day highlights the growing global impact of dementia and the urgent need for better approaches to prevention, diagnosis and treatment. While dementia remains one of the greatest healthcare challenges of our time, 2026 marks a pivotal point in its scientific evolution.
For decades, Alzheimer’s disease research was characterised by promising biological hypotheses followed by disappointing late-stage clinical trials. Today, that landscape is changing. Disease-modifying therapies are entering clinical practice, blood-based biomarkers are enabling earlier and more accessible diagnosis, and researchers are increasingly expanding beyond amyloid to target other forms of dementia.
Perhaps most importantly, dementia is no longer being viewed as a single disease. Instead, it is increasingly recognised as a collection of overlapping biological disorders that may require more precise diagnosis and personalised therapeutic approaches.
Anti-amyloid therapy has changed the development paradigm
The arrival of anti-amyloid monoclonal antibodies has demonstrated that modifying a core component of Alzheimer’s pathology can slow disease progression.
In Australia, donanemab (KISUNLA) was approved by the TGA in May 2025 for selected patients with early symptomatic Alzheimer’s disease, followed by lecanemab (LEQEMBI) in September 2025. These therapies do not reverse established dementia and require careful patient selection, confirmation of amyloid pathology and ongoing safety monitoring. However, both have shown clinically meaningful slowing of disease progression, allowing patients to maintain cognitive function longer than would otherwise be expected.
Their significance extends beyond individual products. They have fundamentally changed the central development question from “Can Alzheimer’s disease be modified?” to “Which pathology should be targeted, in which patient, and at what stage of disease?”
Is tau the next therapeutic frontier?
Attention is increasingly shifting towards tau, a protein closely associated with neurodegeneration and clinical decline.
In 2026, Biogen reported topline results from the Phase 2 CELIA study of diranersen, an antisense oligonucleotide designed to reduce tau production. While the study did not meet its primary endpoint of demonstrating a dose-response effect on the Clinical Dementia Rating-Sum of Boxes, it produced reductions in tau pathology and encouraging signals across cognitive measures.
The findings highlight both the promise and complexity of dementia drug development. Demonstrating robust effects on a biological target does not automatically translate into meaningful clinical benefit. Nevertheless, the study provides important evidence that tau-directed therapies can modify disease-relevant biology in humans and supports continued investigation of tau-targeted and combination treatment approaches.
Blood biomarkers could transform diagnosis and clinical trials
One of the most transformative developments in dementia research is occurring outside therapeutics.
Blood-based biomarkers are rapidly changing how Alzheimer’s pathology can be detected and how patients may be selected for clinical trials. In 2025, the US FDA cleared the first blood-based in vitro diagnostic assay to aid Alzheimer’s disease diagnosis, representing a significant milestone.
Australian evidence is demonstrating clinical utility. A 2026 study across three memory and cognition clinics found that plasma pTau181 testing changed clinicians’ diagnoses in more than 10% of cases and substantially improved diagnostic confidence.
For drug developers, the implications are significant. Blood biomarkers offer the potential to reduce screening costs, improve trial efficiency, identify biologically defined patient populations and potentially provide longitudinal measures of disease progression or treatment response.
Research is also moving from diagnosis towards prediction. Data presented at AAIC 2026 showed that cognitively unimpaired older adults with very high p-tau217 concentrations had an estimated 78% risk of developing cognitive impairment over the following decade. If Alzheimer’s disease can be reliably identified before symptoms emerge, preventive intervention studies become increasingly feasible.
Beyond amyloid and tau
The Alzheimer’s development pipeline is becoming increasingly diverse.
A recent analysis identified 158 drugs across 192 active Alzheimer’s clinical trials. While disease-targeting therapies continue to dominate development, investigational approaches now address inflammation, immune dysfunction, synaptic function, metabolism, vascular biology and proteostasis alongside amyloid and tau.
Importantly, the proportion of the pipeline focused on amyloid has declined over the past decade, while investment in tau and immune-mediated approaches has increased. This reflects growing recognition that Alzheimer’s disease is unlikely to be driven by a single pathological mechanism and may ultimately require multi-target therapeutic strategies.
Precision medicine beyond Alzheimer’s disease
The move towards precision medicine is also evident in other forms of dementia.
Frontotemporal dementia (FTD) is particularly attractive for targeted drug development because genetically defined disease subtypes provide clear biological targets. In September 2026, first-in-human results were reported for VES001, an oral small-molecule therapy designed to address progranulin deficiency in FTD associated with GRN mutations. The study demonstrated blood-brain barrier penetration and increased progranulin concentrations in both plasma and cerebrospinal fluid, providing early proof of mechanism in humans. Although clinical efficacy remains to be established, the results highlight the growing trend towards therapies designed for specific molecular subtypes of neurodegenerative disease.
What does this mean for clinical development?
Dementia development is becoming increasingly biomarker-driven and biologically informed.
Half of active Alzheimer’s trials now incorporate biomarkers for participant selection, while more than a quarter include biomarkers as primary outcome measures. As a result, biomarker strategy can no longer be considered a secondary scientific consideration. Assay validation, laboratory capability, genetic testing, imaging access and regulatory acceptance increasingly influence study feasibility, recruitment and interpretation.
The next phase of dementia research is unlikely to be defined by a single therapeutic breakthrough. Instead, the field is beginning to resemble other areas of precision medicine: identifying the underlying pathology, determining disease stage and matching patients to the most appropriate intervention.
For organisations developing therapeutics, diagnostics and enabling technologies in neurodegenerative disease, the challenge is increasingly one of integration. Scientific discovery, clinical development and regulatory strategy must evolve together to translate emerging biological insights into meaningful patient outcomes.
Are you prepared for the next generation of neurodegenerative disease development?
Contact Adjutor to explore how we can support biomarker-driven clinical development, regulatory strategy and precision medicine approaches across dementia and neurodegenerative disease programs.
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