Longitudinal biomarker studies in human neuroimaging: capturing biological change of Alzheimer’s pathology
Despite extensive research, open questions about the biological underpinnings of Alzheimer’s disease (AD) remain. Neuroimaging biomarkers based on positron emission tomography (PET) and magnetic resonance imaging (MRI) offer in vivo insights into these complex biological changes and interactions. However, most evidence to date comes from cross-sectional studies, limiting our understanding of disease progression. Longitudinal studies enable the investigation of biological changes within individuals, revealing how pathology evolves over time. With this review, we provide an overview of how longitudinal imaging biomarker studies have advanced the field and how they can contribute to future research. We highlight longitudinal biomarker studies that have provided critical insights into disease trajectories, staging, and individual variability. We further assess longitudinal multimodal studies which have elucidated interactions between AD-specific pathology, amyloid-β and tau, and broader biological changes like neurodegeneration, neuronal dysfunction, vascular disease, and inflammation. Further, we discuss associations of brain changes with symptomatology and clinical outcomes and conclude with challenges and future directions.
Authors
- Lyduine E. Collij (ORCID: https://orcid.org/0000-0001-6263-1762)
- Michel J. Grothe (ORCID: https://orcid.org/0000-0003-2600-9022)
- Maura Malpetti (ORCID: https://orcid.org/0000-0001-8923-9656)
- Samira A. Maboudian (ORCID: https://orcid.org/0000-0003-4929-775X)
- Nick C. Fox (ORCID: https://orcid.org/0000-0002-6660-657X)
- Serena Capelli (ORCID: https://orcid.org/0000-0002-8450-3806)
- L. Annen
- Anne Maaß (ORCID: https://orcid.org/0000-0002-7889-795X)
- Paul Edison
- Aitana Sogorb‐Esteve (ORCID: https://orcid.org/0000-0002-7869-8192)
- Larissa Fischer (ORCID: https://orcid.org/0009-0001-9936-2954)
- Prithvi Arunachalam (ORCID: https://orcid.org/0000-0002-0798-6250)
- Dana Parker (ORCID: https://orcid.org/0000-0002-9822-412X)
- William J. Jagust (ORCID: https://orcid.org/0000-0002-4458-113X)
- Corrina Fonseca (ORCID: https://orcid.org/0000-0002-4156-1037)
- Ross W. Paterson (ORCID: https://orcid.org/0000-0001-9372-3635)
- Michael Schöll (ORCID: https://orcid.org/0000-0001-7800-1781)
- Nicolai Franzmeier (ORCID: https://orcid.org/0000-0001-9736-2283)
- Michelle Barboure
- Julia R. Bacci (ORCID: https://orcid.org/0009-0005-7408-0984)
- Claudia Tato-Fernández (ORCID: https://orcid.org/0009-0008-8448-8678)
- Stamatia Karagianni (ORCID: https://orcid.org/0009-0006-2505-770X)
Institutions
- University of Geneva (CH)
- University of Turku (FI)
- Lund University (SE)
- Mario Negri Institute for Pharmacological Research (IT)
- University of California, Irvine (US)
- University of Cambridge (GB)
- Sahlgrenska University Hospital (SE)
- Instituto de Salud Carlos III (ES)
- German Center for Neurodegenerative Diseases (DE)
- Turku University Hospital (FI)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- LMU Klinikum (DE)
- Turku PET Centre (FI)
- University Hospital of Geneva (CH)
- Amsterdam Neuroscience (NL)
- Munich Cluster for Systems Neurology (DE)
- UK Dementia Research Institute (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Fundacion Centro De Investigacion De Enfermedades Neurologicas (ES)
- University College London (GB)
- Wake Forest University (US)
- Imperial College London (GB)
- Geneva College (US)
- Cardiff University (GB)
- Ludwig-Maximilians-Universität München (DE)
- Vrije Universiteit Amsterdam (NL)
- University of Gothenburg (SE)
- University of California, Berkeley (US)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- Alzheimer s Research & Therapy
- Published
- 2025-12-04
- DOI
- https://doi.org/10.1186/s13195-025-01920-6
- Citations
- 2
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 2.94