Diagnostic Workup
Adding biomarker evidence to your existing algorithm may help increase your confidence in diagnosing Alzheimer’s disease (AD)1,2
Blood-based biomarkers could be a key step in a diagnostic process that begins in primary care and helps to identify individuals who should be referred to specialists for further evaluation, including PET imaging or CSF analysis.3
Other routine diagnostic tools used in the assessment of patients include12,13:
- Routine labs (such as CBC, metabolic panel, LFTs, TSH, vitamin B12, folate)
- Structural imaging (CT scan, MRI)
- Neuropsychological assessment
- FDG-PET scan
Aβ=amyloid beta; AUR=appropriate use recommendations; CBC=complete blood count; CSF=cerebrospinal fluid; CT=computed tomography; FDG-PET=fluorodeoxyglucose-positron emission tomography; GFAP=glial fibrillary acidic protein; LFT=liver function test; MRI=magnetic resonance imaging; NfL=neurofilament light; NFT=neurofibrillary tangle; PET=positron emission tomography; P-tau=phosphorylated tau; TSH=thyroid-stimulating hormone.
Biomarker testing may increase the confidence in your AD diagnosis in patients with cognitive impairment and help inform patient care14,15
FDA-approved amyloid-targeting therapies require the confirmation of amyloid pathology and diagnosis of early symptomatic AD to initiate treatment.16
Biomarker testing in the diagnosis of AD:
- Is designed to identify neuropathological components of AD, in order to differentiate it from other neurodegenerative diseases and normal aging14
- May help provide a neuropathological diagnosis of AD and make services available for patients with suspected AD17
- May increase clinician confidence in your AD diagnosis in patients with cognitive impairment and help inform patient care14,15
Diagnostic uncertainty was reduced from 72% prior to amyloid PET to 16% post-amyloid PET scan1,2
Implementing blood biomarker tests
Implementing AD blood biomarker tests in your clinical practice
- Collect a blood sample according to manufacturer instructions. Be sure to closely adhere to these instructions
- Follow the manufacturer’s guidance on how to store and ship the sample to the testing lab for analysis
Commercially available blood biomarker tests in the US18-22
Test Name
|
Biomarker Tested
|
Developer
|
|---|---|---|
| Test Name PrecivityAD®a | Biomarker Tested | Developer C2N Diagnostics |
| Test Name PrecivityAD2™a | Biomarker Tested | Developer C2N Diagnostics |
| Test Name Quest AD-Detect® | Biomarker Tested | Developer Quest Diagnostics |
| Test Name LucentAD | Biomarker Tested | Developer Lucent Diagnostics |
| Test Name P-tau181 | Biomarker Tested | Developer Labcorp and Quanterix |
Disclaimer: This list is not all-inclusive and does not represent all laboratory vendors and kits. This list is intended for informational purposes and your consideration only, and is based on publicly available information as of October 20, 2023 for these organizations. Eli Lilly and Company (Lilly) makes no representations regarding the clinical or analytical validity, manufacturing quality, or design of the testing offered by the vendors included on this list. Inclusion on this list does not represent an endorsement, referral, or recommendation by Lilly. Contact the laboratory vendor for more information.
The biomarker report of the findings will be provided after the necessary information is submitted to the lab.
aThe APS was developed using C2N’s proprietary algorithm, and it reflects the likelihood that a patient will be amyloid positive on an amyloid PET scan.19
APOE=apolipoprotein E; APS=amyloid probability score; N-P-tau=N-terminal directed P-tau217.
Implementing CSF biomarker tests
Implementing CSF biomarker tests for AD in your clinical practice23,24
- CSF sample is collected using an atraumatic needle via a lumbar puncture
- Guidelines should be enforced for post-collection centrifugation, storage, and shipping
Commercially available CSF tests in the US18
Test Name
|
Biomarker Tested
|
Developer
|
|---|---|---|
| Test Name Elecsys® AD | Biomarker Tested | Developer Roche Diagnostics |
| Test Name ADmark® | Biomarker Tested | Developer Athena Diagnostics |
| Test Name Lumipulse® G | Biomarker Tested | Developer Fujirebio |
Disclaimer: This list is not all-inclusive and does not represent all biomarker tests. This list is intended for informational purposes and your consideration only, and is based on publicly available information as of October 20, 2023 for these organizations. Eli Lilly and Company (Lilly) makes no representations regarding the clinical or analytical validity, manufacturing quality, or design of the testing offered by the vendors included on this list. Inclusion on this list does not represent an endorsement, referral, or recommendation by Lilly. Contact the laboratory vendor for more information.
The results of each of these tests will indicate whether the patient may have neuropathology consistent with AD, or if a conclusive result cannot be determined.
Implementing amyloid and tau PET scans
PET scan overview
- Patient receives tracer injection
- Allow time for tracer uptake
- Complete PET scan
- Imaging physician will read scan and send report* to your office
Commercially available PET tracers in the US18
Imaging Agent
|
Imaging Target
|
Manufacturer
|
|---|---|---|
| Imaging Agent Amyvid® (florbetapir F 18 injection) | Imaging Target Brain amyloid neuritic plaque | Manufacturer Eli Lilly and Company |
| Imaging Agent Neuraceq® (florbetaben F 18 injection) | Imaging Target Brain amyloid neuritic plaque | Manufacturer Life Molecular Imaging |
| Imaging Agent Vizamyl™ (flutemetamol F 18 injection) | Imaging Target Brain amyloid neuritic plaque | Manufacturer GE Healthcare |
| Imaging Agent TAUVID™ (flortaucipir F 18 injection) | Imaging Target Brain tau NFTs | Manufacturer Eli Lilly and Company |
Disclaimer: This list is not all-inclusive and does not represent all biomarker tests. This list is intended for informational purposes and your consideration only, and is based on publicly available information as of January 16, 2024 for these organizations. Eli Lilly and Company (Lilly) makes no representations regarding the clinical or analytical validity, manufacturing quality, or design of the testing offered by the vendors included on this list. Inclusion on this list does not represent an endorsement, referral, or recommendation by Lilly. Contact the radiopharmacy for more information.
Please refer to the manufacturer's PI for full information on Administration, Acquisition Guidelines, and Image Display & Interpretation.
*The report provides a full write-up of the findings, which may indicate whether the scan was positive or negative for the specific pathology.
Please see below for Indication and Important Safety Information for Amyvid (florbetapir F 18 injection) and TAUVID (flortaucipir F 18 injection)
Please see below for Indication and Important Safety Information for Amyvid (florbetapir F 18 injection) and TAUVID (flortaucipir F18 injection)
Indication for Amyvid (florbetapir F 18 Injection)
Amyvid is a radioactive diagnostic agent for Positron Emission Tomography (PET) imaging of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD) and other causes of cognitive decline.
A negative Amyvid scan indicates sparse to no neuritic plaques and is inconsistent with a neuropathological diagnosis of AD at the time of image acquisition; a negative scan result reduces the likelihood that a patient’s cognitive impairment is due to AD. A positive Amyvid scan indicates moderate to frequent amyloid neuritic plaques; neuropathological examination has shown this amount of amyloid neuritic plaque is present in patients with AD, but may also be present in patients with other types of neurologic conditions as well as older people with normal cognition. Amyvid is an adjunct to other diagnostic evaluations.
- Amyvid for intravenous use is supplied in multidose vials containing 500-1900 MBq/mL florbetapir F 18.
Limitations of Use
- A positive Amyvid scan does not establish a diagnosis of AD or other cognitive disorder
-
Safety and effectiveness of Amyvid have not been established for:
- Predicting development of dementia or other neurologic condition
- Monitoring responses to therapies
Important Safety Information for Amyvid (florbetapir F 18 injection)
Risk for Image Misinterpretation and Other Errors
- Errors may occur in the Amyvid estimation of brain neuritic plaque density during image interpretation
- Image interpretation should be performed independently of the patient’s clinical information. The use of clinical information in the interpretation of Amyvid images has not been evaluated and may lead to errors. Other errors may be due to extensive brain atrophy that limits the ability to distinguish gray and white matter on the Amyvid scan as well as motion artifacts that distort the image
- Amyvid scan results are indicative of the brain neuritic amyloid plaque content only at the time of image acquisition and a negative scan result does not preclude the development of brain amyloid in the future
Radiation Risk
- Amyvid, similar to other radiopharmaceuticals, contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling to protect patients and health care workers from unintentional radiation exposure
The most common adverse reactions reported in clinical trials were headache (1.8%), musculoskeletal pain (0.7%), blood pressure increased (0.7%), nausea (0.7%), fatigue (0.5%), and injection site reaction (0.5%)
AM HCP ISI 14SEP2022
Indication for TAUVID (flortaucipir F 18 injection)
TAUVID is indicated for use with positron emission tomography (PET) imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD).
Limitations of Use
TAUVID is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy (CTE).
- TAUVID for intravenous (IV) use is supplied in multidose vial containing 300-3700 Mbq/mL flortaucipir F 18
Important Safety Information for TAUVID (flortaucipir F 18 injection)
Risk of Misdiagnosis in Patients Evaluated for Alzheimer’s disease (AD)
TAUVID does not target β-amyloid, one of two required components of the neuropathological diagnosis of AD. TAUVID performance for detecting tau pathology was assessed in terminally ill patients, the majority of whom had AD dementia with B3 level neurofibrillary tangle (NFT) pathology. TAUVID performance for detecting tau pathology may be lower in patients in earlier stages of the pathological spectrum.
Negative TAUVID Scan
NFTs may be present at levels that qualify for the neuropathological diagnosis of AD (B2 tau pathology in the presence of at least moderate levels of cortical amyloid pathology) in patients with a negative TAUVID scan. Consider additional evaluation to confirm the absence of AD pathology in patients with a negative TAUVID scan.
False Positive TAUVID Scan
Small foci of noncontiguous tracer uptake may lead to a false positive TAUVID scan. Only uptake of tracer in the neocortex should contribute to the interpretation of a positive TAUVID scan.
Risk of Chronic Traumatic Encephalopathy Misdiagnosis
The safety and effectiveness of TAUVID have not been established for patients being evaluated for CTE. Preliminary non-clinical and clinical investigations suggest differences in tau conformation and distribution may limit flortaucipir F 18 binding. Therefore, TAUVID is not indicated for detection of CTE.
Radiation Risk
Diagnostic radiopharmaceuticals, including TAUVID, expose patients to radiation. Radiation exposure is associated with a dosedependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure.
ADVERSE REACTIONS
The most common adverse reactions reported in clinical trials were headache (1.4%), injection site pain (1.2%), and increased blood pressure (0.8%).
USE IN SPECIAL POPULATIONS
Pregnancy
All radiopharmaceuticals, including TAUVID, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. Advise a pregnant woman of the potential risks of fetal exposure to radiation doses with administration of TAUVID.
Lactation
Advise a lactating woman to avoid breastfeeding for 4 hours after TAUVID administration in order to minimize radiation exposure to a breastfed infant.
FT HCP ISI 14SEP2022
Indication for Amyvid (florbetapir F 18 Injection)
Amyvid is a radioactive diagnostic agent for PET imaging of the brain to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD) and other causes of cognitive decline.
A negative Amyvid scan indicates sparse to no neuritic plaques and is inconsistent with a neuropathological diagnosis of AD at the time of image acquisition; a negative scan result reduces the likelihood that a patient’s cognitive impairment is due to AD. A positive Amyvid scan indicates moderate to frequent amyloid neuritic plaques; neuropathological examination has shown this amount of amyloid neuritic plaque is present in patients with AD, but may also be present in patients with other types of neurologic conditions as well as older people with normal cognition. Amyvid is an adjunct to other diagnostic evaluations.
- Amyvid for intravenous use is supplied in multidose vials containing 500-1900 MBq/mL florbetapir F 18.
Limitations of Use
- A positive Amyvid scan does not establish a diagnosis of AD or other cognitive disorder
-
Safety and effectiveness of Amyvid have not been established for:
- Predicting development of dementia or other neurologic condition
- Monitoring responses to therapies
Indication for TAUVID (flortaucipir F 18 injection)
TAUVID is indicated for use with positron emission tomography (PET) imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD).
Limitations of Use
TAUVID is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy (CTE).
- TAUVID for intravenous (IV) use is supplied in multidose vial containing 300-3700 Mbq/mL flortaucipir F 18
Important Safety Information for Amyvid (florbetapir F 18 injection)
Risk for Image Misinterpretation and Other Errors
- Errors may occur in the Amyvid estimation of brain neuritic plaque density during image interpretation
- Image interpretation should be performed independently of the patient’s clinical information. The use of clinical information in the interpretation of Amyvid images has not been evaluated and may lead to errors. Other errors may be due to extensive brain atrophy that limits the ability to distinguish gray and white matter on the Amyvid scan as well as motion artifacts that distort the image
- Amyvid scan results are indicative of the brain neuritic amyloid plaque content only at the time of image acquisition and a negative scan result does not preclude the development of brain amyloid in the future
Radiation Risk
- Amyvid, similar to other radiopharmaceuticals, contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk of cancer. Ensure safe handling to protect patients and health care workers from unintentional radiation exposure
The most common adverse reactions reported in clinical trials were headache (1.8%), musculoskeletal pain (0.7%), blood pressure increased (0.7%), nausea (0.7%), fatigue (0.5%), and injection site reaction (0.5%)
AM HCP ISI 14SEP2022
Important Safety Information for TAUVID (flortaucipir F 18 injection)
Risk of Misdiagnosis in Patients Evaluated for Alzheimer’s disease (AD)
TAUVID does not target β-amyloid, one of two required components of the neuropathological diagnosis of AD. TAUVID performance for detecting tau pathology was assessed in terminally ill patients, the majority of whom had AD dementia with B3 level neurofibrillary tangle (NFT) pathology. TAUVID performance for detecting tau pathology may be lower in patients in earlier stages of the pathological spectrum.
Negative TAUVID Scan
NFTs may be present at levels that qualify for the neuropathological diagnosis of AD (B2 tau pathology in the presence of at least moderate levels of cortical amyloid pathology) in patients with a negative TAUVID scan. Consider additional evaluation to confirm the absence of AD pathology in patients with a negative TAUVID scan.
False Positive TAUVID Scan
Small foci of noncontiguous tracer uptake may lead to a false positive TAUVID scan. Only uptake of tracer in the neocortex should contribute to the interpretation of a positive TAUVID scan.
Risk of Chronic Traumatic Encephalopathy Misdiagnosis
The safety and effectiveness of TAUVID have not been established for patients being evaluated for CTE. Preliminary non-clinical and clinical investigations suggest differences in tau conformation and distribution may limit flortaucipir F 18 binding. Therefore, TAUVID is not indicated for detection of CTE.
Radiation Risk
Diagnostic radiopharmaceuticals, including TAUVID, expose patients to radiation. Radiation exposure is associated with a dosedependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure.
ADVERSE REACTIONS
The most common adverse reactions reported in clinical trials were headache (1.4%), injection site pain (1.2%), and increased blood pressure (0.8%).
USE IN SPECIAL POPULATIONS
Pregnancy
All radiopharmaceuticals, including TAUVID, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of radiation dose. Advise a pregnant woman of the potential risks of fetal exposure to radiation doses with administration of TAUVID.
Lactation
Advise a lactating woman to avoid breastfeeding for 4 hours after TAUVID administration in order to minimize radiation exposure to a breastfed infant.
FT HCP ISI 14SEP2022
At Lilly, we are committed to partnering with you to improve the diagnostic journey for patients in the early stages of AD
Dive deeper into practical suggestions for effective AD care implementation.*
LEARN MORE*This article was published prior to the FDA approval of amyloid-targeting therapies.
Other product/company names mentioned herein are the trademarks of their respective owners.
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- Porteri C, Albanese E, Scerri C, et al; Geneva Task Force for the Roadmap of Alzheimer’s Biomarkers. The biomarker-based diagnosis of Alzheimer’s disease. 1—ethical and societal issues. Neurobiol Aging. 2017;52:132-140.
- Iaccarino L, Burnham SC, Dell’Agnello G, et al. Diagnostic biomarkers of amyloid and tau pathology in Alzheimer’s disease: an overview of tests for clinical practice in the United States and Europe. J Prev Alzheimers Dis. 2023;10(3):426-442.
- Precivity™. PrecivityAD®. Accessed October 18, 2023. https://precivityad.com/healthcare-providers
- Quest Diagnostics™. Quest AD-Detect®, Beta-Amyloid 42/40 Ratio, Plasma. Updated October 2023. Accessed October 18, 2023. https://testdirectory.questdiagnostics.com/test/test-guides/TS_AD_Detect_BetaRatioPlasma/quest-ad-detect-beta-amyloid-4240-ratio-plasma?p=td
- Lucent Diagnostics. LucentAD Test Specs. Accessed October 20, 2023. https://www.lucentdiagnostics.com/wp-content/uploads/2023/06/LucentAD_Test-Specs_6302023v2.pdf
- Labcorp. Phosphorylated Tau 181 (pTau-181), Plasma. Accessed October 20, 2023. https://www.labcorp.com/tests/483745/phosphorylated-tau-181-ptau-181-plasma
- Hampel H, Shaw LM, Aisen P, et al. State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer’s disease. Alzheimers Dement. 2022;18(1):159-177.
- Hansson O, Rutz S, Zetterberg H, et al. Pre-analytical protocol for measuring Alzheimer’s disease biomarkers in fresh CSF. Alzheimer’s Dement (Amst). Published online December 8, 2020. doi:10.1002/dad2.12137