Beta amyloid 42/40 is a biomarker for cerebral beta amyloid pathology1. A low beta amyloid 42/40 ratio reflects selective depletion of beta amyloid 42 due to the deposition in amyloid plaques in the brain. A low 42/40 ratio can also be due to amyloid deposition in the blood vessels due to cerebral amyloid angiopathy.
Test code(s): 11786, 12563, 13825, 13690, 94627, 94628, 92433, 10642
- Quest AD-Detect® Beta-Amyloid 42/40 Ratio, Plasma (11786)
- Quest AD-Detect® Apolipoprotein E (ApoE) Isoform, Plasma (12563)
- Quest AD-Detect® Phosphorylated tau217 (p-tau217), Plasma (13825)
- Quest AD-Detect® Phosphorylated tau181 (p-tau181), Plasma (13690)
- Neurofilament Light Chain, Plasma (13979)
- Beta-Amyloid 42/40 Ratio, CSF (94627)
- Beta-Amyloid 42/40 Ratio and Apolipoprotein E (ApoE) Isoform Panel, CSF (94628)
- ADmark® Phospho-Tau/Total-Tau/A Beta42, Analysis and Interp, CSF (Symptomatic) (92433)
- ADmark® ApoE Genotype Analysis and Interpretation (Symptomatic) (10642)
- Quest AD-Detect® Beta-Amyloid 42/40 Ratio, Plasma (11786)
- Quest AD-Detect® Apolipoprotein E (ApoE) Isoform, Plasma (12563)
- Beta-Amyloid 42/40 Ratio, CSF (94627)
- Beta-Amyloid 42/40 Ratio and Apolipoprotein E (ApoE) Isoform Panel, CSF (94628)
- ADmark® Phospho-Tau/Total-Tau/A Beta42, Analysis and Interp, CSF (Symptomatic) (92433)
The combination of beta amyloid 42/40 and p-tau181 are utilized to detect AD pathology changes (amyloid plaques and neurofibrillary tangles) characteristic of Alzheimer’s disease. The presence of beta amyloid in the absence of a positive p-tau181 result typically occurs early in the Alzheimer’s disease continuum.
A beta amyloid ratio below 0.160 indicates a higher likelihood of having a positive amyloid PET scan. In a memory clinic cohort, a beta amyloid ratio of 0.169 to 0.160 correlated with 15% of patients having a positive amyloid PET scan, while a ratio of 0.159 to 0.150 correlated with an 85% chance of patients having a positive amyloid PET scan1.
The presence of APOE e4, particularly in patients who are homozygotes, indicates an increased risk for the development of ARIA with anti-amyloid treatment2.
A borderline CSF result typically is the result of a patient with underlying amyloid pathology, but the test result is more consistent with having mild cognitive impairment (MCI) rather than with full-blown Alzheimer’s disease3.
Patients with a positive beta amyloid 42/40 ratio and a negative PET scan are often earlier in the disease continuum. A recent study showed that patients with a positive 42/40 ratio and a negative PET scan are consistent with AD pathology on MRI4.
References
- Weber DM, Taylor SW, Lagier RJ et al. Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer’s disease assessment. Frontiers in Neurology. 2024;15:1364658. doi: 10.3389/fneur.2024.1364658
- Sperling RA, Jack CR, Black SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement. 2011;7(4):367-385. doi:10.1016/j.jalz.2011.05.2351
- Reimand J, Boon BDC, Collij LE, et al. Amyloid-beta PET and CSF in an autopsy-confirmed cohort. Ann Clin Trans Neurol. 7(11):2150-2160. doi:10.1002/acn3.51195
- DeSimone JC, Wang WE, Lowenstein DA, et al. Diffusion MRI relates to plasma Abeta42/40 in PET negative participants without dementia. Alzheimers Dement. 2024;20(4):2830-2842. doi:10.1002/alz.13693
This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.
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