New ways of thinking about Alzheimer’s diseaseAlzheimer’s disease (AD) is highly prevalent, and its incidence is expected to double by 2050.1 Understanding the disease through early diagnosis and differentiating it from other forms of dementia can be helpful for physicians and patients.

Researchers and clinicians have long recognized the extensive clinical, biological, pathological, and genetic variations found in AD patients. What’s generally agreed is that an accurate, personalized risk assessment is needed. Such an assessment can lead to a more effective disease management strategy, specifically customized to the individual.

Recently, new approaches to assessing the likelihood that a patient has AD have been developed. Diagnostic tests for early detection include measuring Abeta 42 (Aß42), a known biomarker of AD. The new approach involves measuring Abeta 42/Abeta 40 (Aß42/Aß40) ratio, which normalizes results, reducing inter-patient variability.2 The Aß42/Aß40 ratio has been reported to have better sensitivity and specificity than Aß42 alone for differentiating mild cognitive impairment and AD from other forms of dementia.2*

Evaluating AD biomarkers with this new methodology may help clarify the relative likelihood of AD, which could lead to better patient management. Although AD is currently not curable, drugs may be used to temporarily alleviate memory loss and confusion. In addition, early diagnosis allows patients to prepare for future care, or choose to participate in clinical trials for new therapies. Ruling out AD expedites investigation of other causes of dementia, including those that may be completely or partially reversed.

Risk Assessment Score

Component Reference Range

Aß42/Aß40 biomarker ratio

> 0.25: Lower risk0.20 – 0.25: Average risk

< 0.20: Higher risk

Analytical measurement ranges:Aß42: 250 – 25,000 pg/mLAß40: 250 – 25,000 pg/mL

ApoE phenotype based on isoforms (E2, E3, E4) corresponding to alleles (ε2, ε3, ε4)

E2/E2: Compared to the most common combination of ApoE isoforms (E3/E3), the E2/E2 combination of isoforms suggests a lower risk of Alzheimer’s disease.

E2/E3: Compared to the most common combination of ApoE isoforms (E3/E3), the E2/E3 combination of isoforms suggests a lower risk of Alzheimer’s disease.3,4

E3/E3: This combination of isoforms is most common and suggests an average risk of Alzheimer’s disease.3,4

E2/E4: Compared to the most common combination of ApoE isoforms (E3/E3), the E2/E4 combination of isoforms suggests a higher risk of Alzheimer’s disease.3,4

E3/E4: Compared to the most common combination of ApoE isoforms (E3/E3), the E3/E4 combination of isoforms suggests a higher risk of Alzheimer’s disease.3,4

E4/E4: Compared to the most common combination of ApoE isoforms (E3/E3), the E4/E4 combination of isoforms suggests a higher risk of Alzheimer’s disease. Of all the isoform combinations, studies suggest that presence of E4/E4 may confer highest risk.3,4

Gender, environment, race, ethnicity, and presence of other risk alleles also contribute to the risk of AD associated with ApoE isoform.3,4

Total ApoE

No reference range is given, since the ApoE values reported in different studies and populations vary widely.5 The individual patient’s ApoE level is used in the development of their risk assessment score.

Risk Assessment Score (risk of having AD)

< -0.918: Lower risk -0.918 – 1.419: Average risk> 1.419: Higher risk

Models used for illustrative purposes.

References1. Alzheimer’s Association. 2017 Alzheimer’s Disease Facts and Figures. Alzheimer’s Dement 2017;13:325-373.2. Janelidze S, Zetterberg H, Mattsson N, et al. CSF Aß42/Aß40 and Aß42/Aß38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol. 2016;3:154-165.3. Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and

Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278:1349-1356.4. Maiti TK, Konar S, Bir S, et al. Role of apolipoprotein E polymorphism as a prognostic marker in traumatic brain injury and neurodegenerative disease: a critical review. Neurosurg Focus.

2015;39:E3.5. Siest G, Pillot T, Régis-Bailly A, et al. Apolipoprotein E: an important gene and protein to follow in laboratory medicine. Clin Chem. 1995;41:1068-1086.* Data on file.** The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party.

QuestDiagnostics.comQuest, Quest Diagnostics, any associated logos, and all associated Quest Diagnostics registered or unregistered trademarks are the property of Quest Diagnostics.All third-party marks—® and ™—are the property of their respective owners. ©2017 Quest Diagnostics Incorporated. All rights reserved. SB6876 5/2017

Alzheimer’s disease

Beta-Amyloid 42/40 Ratio ApoE IsoformBeta-Amyloid 42/40 Ratio, ApoE Isoform and Total ApoE Panel

Test Alias • Beta Amyloid

• ABeta 42

• ABeta 40

• Aß40

• Aß42

• Alzheimer’s disease (AD)

• Apolipoprotein E

• ApoE2

• ApoE3

• ApoE4

• Alzheimer’s disease (AD)

• Beta Amyloid

• ABeta 42

• ABeta 40

• Aß40

• Aß42

• Apolipoprotein E

• ApoE2

• ApoE3

• ApoE4

• Alzheimer’s disease (AD)

Clinical Significance

This LC-MS/MS assay measures beta-amyloid 40 (Aß40) as well as Aß42 in cerebrospinal fluid (CSF), rather than Aß42 alone. This permits the normalization of beta amyloid levels circulating in CSF in different patients. Using the ratio of beta-amyloid 42/beta-amyloid 40, improves sensitivity and specificity for detecting Alzheimer’s disease.2

This LC-MS/MS assay identifies the ApoE isoform(s) in CSF. This information can aid in assessing likelihood of AD.3,4

This panel of LC/MS/MS assays measures Beta-Amyloid 42/40 Ratio and ApoE Isoform and Total ApoE in CSF. Test results are further analyzed by an algorithm that calculates a risk assessment score. Based on this score, patients are categorized as low, intermediate, or high risk of having AD.

Test Code 94627 94626 94628

CPT Codes** 82542 82542 82542 ×2, 82172

Specimen Requirements

Preferred: 1.2 mL (0.6 mL minimum) CSF collected in Polypropylene Collection Container

Preferred: 0.4 mL (0.2 mL minimum) CSF collected in Polypropylene Collection Container

Preferred: 1.6 mL (0.8 mL minimum) CSF collected in Polypropylene Collection Container

Transport Temperature

Frozen Frozen Frozen

Turnaround Time

3–10 days 3–10 days 5–12 days

Quest Diagnostics offers unique insight into the likelihood that a patient’s mild cognitive impairment represents AD, with a family of informative tests.

For more information on AD Biomarkers, call 1.800.NICHOLS (1.800.642.4657) or visit QuestDiagnostics.com/AD