Quest Dementia Testing

While these tests can only be ordered individually at this time, the combination of beta amyloid 42/40 and p-tau181 can be 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-tau 181 result typically occurs early in the Alzheimer’s disease continuum.

While beta amyloid 42/40 and p-tau217 can be ordered individually, the combination of both tests can be utilized to generate a likelihood score for amyloid pathology as measured by a PET scan. The presence of a low beta amyloid 42/40 ratio in the absence of a positive p-tau217 result typically occurs early in the Alzheimer’s disease continuum. A positive p-tau217 in the absence of a low beta amyloid 42/40 can also occur in other neurodegenerative  disorders, usually at levels lower than what is observed in Alzheimer’s disease. 

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 scan.¹

The presence of APOE e4, particularly in patients who are homozygotes, indicates an increased risk for the development of ARIA with anti-amyloid treatment.²

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 disease.³

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 MRI.⁴

In response to neurodegenerative diseases, such as Alzheimer’s disease, astrocytes become reactive and are found around amyloid plaque, suggesting their involvement in amyloid pathology and neuroinflammation.  

GFAP testing can be used in the diagnosis, prognosis, and monitoring of Alzheimer’s disease. Of interest, plasma GFAP has superior diagnostic accuracy when compared to GFAP measured in the spinal fluid.⁷

NfL is a nonspecific axonal marker of neurodegeneration for a number of neurologic diseases, including Alzheimer's disease, multiple sclerosis, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), among others. 

By utilizing an algorithm that combines both beta amyloid 42/40 and pTau 217, one can achieve a likelihood score of amyloid PET scan positivity with 90% sensitivity and 90% specificity. This panel utilizes 2 cut points with less than 20% of patients in the indeterminant zone, which meets CEOi (Global CEO Initiative on Alzheimer’s Disease) guidelines⁶ for utilizing plasma testing in the diagnosis of Alzheimer’s disease.