2025 Volume 11 Pages 26-35
Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID) are the leading causes of dementia, and are characterized by distinct yet overlapping pathophysiological mechanisms. AD is characterized by amyloid-beta plaques, neurofibrillary tangles, and neurodegeneration, whereas VCID arises from vascular damage, including small vessel disease and blood-brain barrier disruption. Biomarkers have revolutionized dementia research and offer tools for early diagnosis, monitoring, and therapeutic evaluation. Cerebrospinal fluid (CSF) biomarkers, such as amyloid-beta (Aβ) 42/Aβ40 ratio and phosphorylated tau, provide reliable indicators of AD pathology, while emerging markers like microtubule binding region (MTBR)-tau243 offer insights into disease progression. Blood-based biomarkers, including plasma Aβ42/Aβ40 ratio, phosphorylated tau, neurofilament light chain (NfL), and glial fibrillary acidic protein, represent scalable, non-invasive alternatives. In VCID, biomarkers like matrix metalloproteinases, soluble platelet-derived growth factor receptor-β and inflammatory markers reflect vascular pathology and neurodegeneration. Advances in detection technologies such as single-molecule arrays have improved sensitivity and precision, facilitating their integration into clinical practice. However, challenges remain, including assay variability, limited accessibility, and high costs. Harmonization of protocols and integration of multimodal biomarkers, including CSF, blood, and imaging data, offer a holistic approach to diagnostics. Biomarkers are central to personalized medicine, enabling tailored interventions and improving the outcomes of patients with dementia. Ongoing innovation holds promise for advancing the understanding and management of these complex disorders.
