Selecting Aβ isoforms for an Alzheimer's disease cerebrospinal fluid biomarker panel

Although the core cerebrospinal fluid Alzheimer's disease (AD) biomarkers amyloid-β (Aβ_1-42) and tau show a high diagnostic accuracy, there are still limitations due to overlap in the biomarker levels with other neurodegenerative and dementia disorders. During Aβ_1-42 production and clearance in the brain, several other Aβ peptides and amyloid precursor protein fragments are formed that could potentially serve as biomarkers for this ongoing disease process. Therefore, this review will present the current status of the findings for amyloid precursor protein and Aβ peptide isoforms in AD and clinically related disorders. In conclusion, adding new Aβ isoforms to the AD biomarker panel may improve early differential diagnostic accuracy and increase the cerebrospinal fluid biomarker concordance with AD neuropathological findings in the brain.