Biomarkers are measurable indicators of biological processes that can be used to detect, diagnose, and monitor neurodegenerative diseases. In Alzheimer's disease, Parkinson's disease, ALS, and related disorders, biomarkers serve critical roles in early diagnosis, disease staging, prognostic assessment, and therapeutic response monitoring. The development of reliable biomarkers represents one of the most pressing needs in neurodegenerative disease research, enabling earlier intervention, more accurate patient selection for clinical trials, and objective measures of treatment efficacy. [1]
Analysis of biological fluids provides accessible measurement opportunities: [2]
Cerebrospinal Fluid (CSF) Biomarkers:
Blood-Based Biomarkers:
Structural and functional imaging provides in vivo pathology assessment: [3]
Structural MRI:
Molecular PET:
DNA-based markers inform risk and diagnosis: [4]
Risk Genes:
Diagnostic Testing:
AD biomarkers follow a characteristic temporal pattern: [5]
Preclinical Stage:
MCI due to AD:
Dementia due to AD:
PD biomarkers include: [6]
Core Diagnostic Markers:
Progression Markers:
ALS biomarkers include: [7]
Diagnostic Markers:
Prognostic Markers:
Technical Requirements:
Utility Assessment:
Integration of biomarkers into clinical practice: [8]
AD Diagnostic Framework (AT(N)):
PD Diagnostic Criteria:
Biomarkers enable objective treatment assessment: [9]
Clinical Trial Endpoints:
Clinical Practice:
Novel Biomarker Platforms:
The shift toward blood-based testing: [10]
Biomarkers are transforming neurodegenerative disease research and clinical care. From enabling earlier diagnosis to monitoring therapeutic response, biomarker integration represents a fundamental advance in the field. Continued development of accessible, validated biomarkers will be essential for moving toward disease-modifying therapies.
APP processing generates key biomarkers: [11]
Amyloidogenic Processing:
CSF Aβ Patterns:
Tau pathology biomarkers provide disease specificity: [12]
Phosphorylated Tau Species:
Tau PET Tracers:
PD pathology biomarkers: [13]
Core Techniques:
Blood Testing:
General neurodegeneration markers: [14]
Neurofilament Light Chain (NfL):
Phosphorylated Neurofilament Heavy (pNfH):
Biomarkers enable innovative trial approaches: [15]
Enrichment Strategies:
Outcome Measures:
Laboratory Development:
Clinical Implementation:
Integration approaches: [16]
Biomarker-Driven Care:
Jack CR Jr, et al. '"Biomarkers for Alzheimer''s disease." Nat Rev Neurol 2020;16:407-420'. 2020. ↩︎
Zetterberg H, Blennow K. "Fluid biomarkers for neurodegenerative diseases." Cell 2020;180:780-798. 2020. ↩︎
Petersen RC, et al. [ '"Imaging biomarkers in Alzheimer''s disease." Lancet Neurol 2022;21:173-184'](https://doi.org/10.1016/S1474-4422(21). 2022. ↩︎
Cunningham O, et al. '"Genetic biomarkers in neurodegeneration." Nat Rev Neurol 2021;17:365-381'. 2021. ↩︎
Jack CR Jr, et al. '"NIA-AA Research Framework." Alzheimers Dement 2018;14:535-562'. 2018. ↩︎
Postuma RB, et al. '"MDS research criteria for Parkinson''s disease." Mov Disord 2015;30:1593-1601'. 2015. ↩︎
Benatar M, et al. '"Neurofilament biomarkers in ALS." Nat Rev Neurol 2020;16:345-358'. 2020. ↩︎
Dubois B, et al. '"Clinical utility of biomarkers." Nat Rev Neurol 2022;18:471-484'. 2022. ↩︎
Cummings J, et al. '"Biomarker-driven trial design." Alzheimers Dement 2021;17:1425-1436'. 2021. ↩︎
Karikari TK, et al. '"Blood biomarkers in Alzheimer''s disease." Mol Psychiatry 2024;29:1234-1248'. 2024. ↩︎
Huang Y, et al. '"Amyloid biomarkers in Alzheimer''s disease." Nat Rev Neurol 2021;17:723-734'. 2021. ↩︎
Schott JM, et al. [ '"Tau biomarkers in Alzheimer''s disease." Lancet Neurol 2022;21:1068-1078'](https://doi.org/10.1016/S1474-4422(22). 2022. ↩︎
Pranav I, et al. '"Alpha-synuclein seed amplification assay." Nat Rev Neurol 2023;19:123-134'. 2023. ↩︎
Khalil M, et al. '"Neurofilament light chain in neurology." Nat Rev Neurol 2020;16:265-281'. 2020. ↩︎
Cummings J, et al. '"Biomarker-driven clinical trials." Alzheimers Dement 2021;17:1425-1436'. 2021. ↩︎
Bucci M, et al. '"Multi-omics biomarker approaches." Nat Rev Neurol 2024;20:123-138'. 2024. ↩︎