Novel Biomarkers for Alzheimer’s Disease: Plasma Neurofilament Light and Cerebrospinal Fluid

Table 2

Blood-based biomarkers for Alzheimer’s disease.

Biomarker	Blood/fluid matrix	Observation in AD	Interpretation/application
NFL	Blood (plasma or serum)	Increased levels were observed in Alzheimer’s disease, familial Alzheimer’s disease, and the early stages of Alzheimer’s disease.	Increased plasma NFL serves as a broad indicator of neurodegeneration, not exclusively linked to Alzheimer’s disease.; It could potentially serve as a screening tool for detecting general neurodegeneration.
Aβ42	CSF	Reduced Aβ42 in Alzheimer’s disease and its early stages (with a sensitivity of over 90%).	Indicates the presence of Aβ accumulation in the brain.; Established as a diagnostic marker with two fully verified mass spectrometry reference measurement procedures (RMP) approved.
	Blood (plasma)	Immunoaffinity-based mass spectrometry (IP-MS) indicates lower levels of plasma Aβ42 in Alzheimer’s disease.; Plasma Aβ42 concentrations exhibit a mild to moderate agreement with amyloid PET.	Indicates amyloid deposition in the brain but is impacted by peripheral expression.; A potential tool for screening purposes.
p-tau	CSF	Increased p-tau is observed in Alzheimer’s disease and its early stages ().	Increased p-tau levels indicate tau’s phosphorylation status, likely reflecting tau pathology in Alzheimer’s disease.; p-tau is more AD-specific compared to T-tau and serves as a diagnostic biomarker.
	Blood (plasma)	Higher p-tau levels appear specific to AD cases with Aβ positivity. There is an association between amyloid PET and tau PET (assessed through MSD assay).	Potential biomarker for diagnosing and screening purposes.
Aβ42/Aβ40	CSF	Reduced Aβ42/Aβ40 ratio is observed in Alzheimer’s disease and its early stages.; Higher accuracy (sensitivity and specificity) compared to Aβ42 alone	The Aβ42/Aβ40 ratio is aimed at adjusting for differences in “total” Aβ production among individuals.; Biomarkers used for diagnosis.
	Blood (plasma)	Simoa and IP-MS show reduced plasma Aβ42/40 in AD and prodromal AD.; Plasma Aβ42/40 ratio moderately aligns with amyloid PET results.	The Aβ42/Aβ40 ratio might indicate cerebral amyloidosis-related mechanisms.; A potential tool for screening.
Neurogranin	CSF	Higher neurogranin was observed in Alzheimer’s and early stages of the disease.	Indicates synaptic dysfunction or degeneration.; Biomarkers used for diagnosis.
T-tau	CSF	Increased T-tau levels are present in Alzheimer’s disease and its early stages (with sensitivity exceeding 90%)	Increased T-tau indicates the severity of neurodegeneration.; Biomarkers used for diagnosis.
	Blood (plasma)	Slight to moderate increases were observed in Alzheimer’s disease and its early stages.	Affected by external or peripheral expression; Not likely to serve as a biomarker in Alzheimer’s disease