Innovative diagnostics accelerating early detection of Alzheimer’s
In the United States, over 6.9 million people live with Alzheimer’s disease (AD), and the number of cases is expected to rise to 13 million by 2050. In fact, one in nine Americans over 65 have Alzheimer’s dementia, the most common form of dementia. In total, the disease has an estimated economic cost on the U.S. economy of $360B.2
After decades waiting for impactful treatments, there’s finally hope. With recent healthcare advancements, having an accurate, confirmed diagnosis early in the disease will enable those affected by AD to take advantage of new therapies and also to make necessary changes to their lifestyle to help delay onset of dementia and/or disease progression. As a result, an accurate, confirmed diagnosis is more important than ever.
Cerebrospinal fluid biomarkers support early diagnosis of Alzheimer’s
Timely diagnosis of Alzheimer’s disease is an unmet need in clinical practice. The diagnosis of Alzheimer’s is often one of exclusion, determined by ruling out non-AD causes of symptoms through several evaluations such as cognitive exams, laboratory tests and neuroimaging. Unfortunately, this process not only could delay the formal diagnosis, but it was shown that clinical diagnosis can be inaccurate in approximately 23% of cases.2,3 The use of cerebrospinal fluid (CSF) biomarkers could positively impact clinical diagnosis for Alzheimer’s disease.
In addition to other clinical investigations, an early Alzheimer’s diagnosis can be supported by CSF biomarker tests that measure beta-amyloid protein (1-42) (Abeta42), phosphorylated tau protein (pTau) and total Tau protein (tTau). Changes in these biomarkers reflect the specific Alzheimer’s pathologies such as the accumulation of abnormal amyloid-beta and tau in plaques, in neurofibrillary tangles, which are followed by neurodegeneration.
Our FDA-cleared Elecsys® Alzheimer’s disease CSF biomarker portfolio can aid in the confirmed diagnosis of Alzheimer’s disease for those with mild cognitive impairment (MCI) and mild Alzheimer’s disease dementia, and can support treatment decisions for patients presenting in these early disease stages.
Early diagnosis can benefit patients and society
An early Alzheimer’s disease diagnosis can lead to patient eligibility for new therapies targeted at early stages of the disease. In addition, it allows patients time to take preventative measures to safeguard their cognitive functions, prolong their ability to live independently and enhance their quality of life. By facilitating access to treatment and management of the disease in early stages, a timely diagnosis could potentially significantly lower the medical and long-term care costs for this disease.2
References
- Elecsys® Method Sheets: ms_08846634501; ms_08821909501; ms_08846715501; ms_08846693501; ms_08821941501.
- Alzheimer’s Association. 2024 Alzheimer’s Disease Facts and Figures. Alzheimer's Dement 2024;20(5).
- Sabbagh MN, Lue LF, Fayard D, Shi J. Increasing Precision of Clinical Diagnosis of Alzheimer’s Disease Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data. Neurol Ther. 2017 Jul;6(Suppl 1):83-95. doi: 10.1007/s40120-017-0069-5.
- Bob Olsson et. al., CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis, The Lancet Neurology, Volume 15, Issue 7, 2016, Pages 673-684
- Hampel H, Hardy J, Blennow K, et al. The Amyloid-β Pathway in Alzheimer's Disease. Mol Psychiatry. 2021;26(10):5481-5503
Alzheimer's disease is a progressive disease, and when patients advance into dementia stages, they need increased assistance from family or caregivers to understand and communicate; perform daily living activities; and manage other health conditions, finances and legal affairs, etc.2
Early diagnosis is key, as access to new therapies and lifestyle interventions can slow down cognitive decline and delay the progression if implemented in early disease stages.3 It also allows patients and their families to plan for the future. It is estimated that each day nearly 2,000 patients ages 65 and older may progress from mild to moderate dementia,4 meaning time is of the essence.
The most complete portfolio of Alzheimer’s cerebrospinal fluid biomarker tests
Roche’s FDA-cleared biomarkers represent all three main Alzheimer’s pathologies – amyloid plaques, tau tangles and neurodegeneration. With these biomarkers, identification of Alzheimer’s disease pathology in early disease stages (as early as mild cognitive impairment), and, therefore treatment is possible.1,3
The Elecsys® Phospho-Tau (181P) CSF (pTau181) and Beta-Amyloid (1-42) CSF II (Abeta 42) and Elecsys® Total Tau CSF (tTau) and Beta-Amyloid (1-42) CSF II (Abeta 42) ratios have high concordance with Beta‑Amyloid positron emission tomography (PET) scan results.4 The Elecsys® Alzheimer’s disease cerebrospinal fluid (CSF) tests combine both Abeta42 and tau proteins to give accurate and reliable results that can confirm amyloid pathology in early stages of the disease5 and aid in Alzheimer’s diagnosis. Compared to a PET scan imaging test in some geographies, these assays are more accessible and cost effective, meaning an accelerated and early path to a confirmed diagnosis is within reach for more people.
Biomarkers for Alzheimer’s disease can be an early indicator of change6,7,8,9,10
The accumulation of abnormal amyloid beta in plaques and tau in neurofibrillary tangles are regarded as the pathological hallmarks of Alzheimer’s.7 Changes in both amyloid and tau proteins start decades prior to symptom onset and can be detected by fluid (e.g., CSF) or imaging (amyloid/tau PET) biomarkers.7,8 In patients presenting with cognitive decline, a positive Elecsys pTau181/Abeta42 CSF ratio or Elecsys tTau/Abeta42 CSF ratio result is consistent with a positive amyloid PET scan result. A positive result does not establish a diagnosis of Alzheimer’s and should always be interpreted in conjunction with clinical information.1
CSF biomarkers for Alzheimer’s disease increase specificity and confidence9
In patients presenting with cognitive decline, biomarkers enhance diagnostic accuracy and physician confidence in early diagnosis.9,10
A prospective, multicenter study evaluating physician surveys demonstrated the value of CSF testing in informing clinical decisions and optimizing patient management. In clinical cases where CSF results were considered, management was modified for 46.4% of patients (71/153), including 36 (23.5%) of patients enrolled in clinical trials. Additionally, the inclusion of CSF testing modified diagnoses, increased AD diagnoses and improved clinician confidence in the Alzheimer’s diagnosis.10
Roche CSF biomarkers for Alzheimer’s disease testing
Roche AD CSF Assays: precision, access and affordability combined
Results are reliable with Elecsys® Beta-Amyloid (1-42) CSF II, Phospho-Tau (181P) CSF and tTau CSF assays.4 The Amyloid beta (1-42) (Abeta42) and phosphorylated tau (pTau181) CSF biomarkers' role is increasingly recognized in supporting Alzheimer’s and MCI diagnosis.11
Confirmation of amyloid pathology via CSF FDA-cleared Alzheimer’s biomarker testing or amyloid PET is recommended in the appropriate use guidelines for new and emerging disease-specific therapies that have shown to slow down cognitive decline when administered in early-disease stages.12
As depicted in the PET visual read classification graph, the pTau181/Abeta42 and the tTau/Abeta42 ratios results were able to distinguish between the amyloid PET classifications of positive and negative.5
Lab implementation
Efficiency through integration
Scalable and economical, all Elecsys® AD CSF assays can be added to any of Roche’s widely-available cobas® fully-automated immunoassay analyzers, giving patients broad access to high-quality testing in a timely manner.
4 reasons to implement the Elecsys® Alzheimer’s disease CSF tests:
Increasing demand
With full approval of AD therapies¹¹, capture the increasing volume and therefore value of these assays for your institution.
Broad access
AD CSF testing can be conducted at laboratories affiliated with outpatient and inpatient settings, which perform lumbar procedures (HCP offices, radiology centers, etc.), pointing to increased demand.
Low cost
The cost for a CSF assay is expected to be much lower than for a PET scan, meaning much-needed help is possible for more people.
Accuracy
The Elecsys® pTau181/Abeta42 and tTau/Abeta42 ratios are traceable to reference materials to ensure accuracy of results. This is reflected in their high overall agreement (89%-90%) with amyloid PET. Including the Elecsys biomarkers in the diagnostic workup have the potential to aid in the clinical diagnosis of AD, especially at early stages of the disease.1,5
References
- Elecsys® Method Sheets: ms_08846634501; ms_08821909501; ms_08846715501; ms_08846693501; ms_08821941501.
- Alzheimer’s Association. 2024 Alzheimer’s Disease Facts and Figures. Alzheimer's Dement 2024;20(5).
- Alzheimer’s Disease International. Accessed June 30, 2023.
- Alzheimer’s Association. Accessed June 30, 2023.
- Hansson O. et al. Alzheimer's Dement. 2018; 14[11]:1470-1481.
- Agamanolis, D. (2020). Alzheimer’s Disease (in Neuropathology). Accessed June 30, 2023.
- Jack CR, et al. Lancet Neurol. 2010;9(1):119-128.
- Bateman, RJ, et al. N Engl J Med. 2012;367(9):795-804.
- Sabbagh, et al, Neurol Ther. 2017 Jul;6(Suppl 1):83-95.
- Cognat E, et al. BMJ Open. 2019;9(5):e026380.
- Bittner T, et al. Alzheimers Dement. 2016;12(5):517-526.
- Cummings, J., Apostolova, L., Rabinovici, G.D. et al. Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis (2023).
With an emerging menu of Research Use Only (RUO) biomarker assays, Roche is committed to investigating and developing the global solutions that will help researchers find answers in the vast and complex area of neurology.
Roche’s Neurology RUO menu currently includes:
| 01 | 02 | 03 | 04 | 05 |
| NfL* Neurofilament light chain |
pTau 181 plasma* Phosphorylated Tau 181 |
pTau 217 plasma* Phosphorylated Tau 181 |
APOE4* Apolipoprotein E |
GFAP* Glial fibrillary acidic protein |
For information on how to partner with Roche in furthering your institution’s neurology research efforts, please fill out the form to the right. A Roche RUO representative will contact you.
Alzheimer’s disease begins to form around 20 years before memory loss or other symptoms develop. However, many people with Alzheimer's are not aware they have it or have not been properly diagnosed. According to the Alzheimer's Association, 85% of people would want to know early if they had the disease.¹
An early and accurate diagnosis is crucial for patients, caregivers and physicians, as it can provide clarity and new treatment options.1,2
Clinical trials and other studies showed that up to 30% of individuals who meet the criteria for clinical Alzheimer’s dementia based on symptoms did not have Alzheimer’s-related brain changes.1 By utilizing biomarkers to support Alzheimer’s diagnosis, especially in early disease stages, the accuracy of clinical diagnosis is expected to increase significantly.3 The need for a more precise diagnosis is now.
Definitions
What are biomarkers?
Biomarkers are biological changes that can be measured to indicate the presence or absence of a disease or the risk of developing a disease. The biomarkers most characteristic to Alzheimer’s are abnormal amyloid beta and tau proteins which accumulate in the brain and are present in the cerebrospinal fluid (CSF).
Therefore, changes in these proteins can be visualized by imaging the brain with scanning techniques, or can be measured in the CSF1,2 using laboratory tests.
For example, the Elecsys CSF ratio assays are FDA cleared laboratory tests designed to detect the level of amyloid-beta protein (1-42) (Abeta42), phosphorylated tau protein 181 (pTau181) and total Tau protein (tTau). The results of these tests are intended to be interpreted by the physicians along with other clinical diagnostic evaluations to support AD diagnosis.4
What is cerebrospinal fluid?
CSF is a fluid that surrounds and protects the brain and spinal cord. CSF contains the abnormal amyloid and tau proteins associated with Alzheimer’s disease (AD). In case of cognitive issues and suspicion of AD, measuring the levels of these proteins from CSF helps with the AD diagnosis process. To collect CSF for testing these specific proteins, a lumbar puncture (spinal tap) is needed.1,2
Early diagnosis of Alzheimer’s is key
The progression of AD occurs along a continuum, starting with preclinical neuropathological changes, including an increasing loss of independence as the disease progresses, and ending with severe Alzheimer's dementia:1-4
Mild cognitive impairment due to Alzheimer’s
Mild symptoms but independence is maintained. Diagnosing people at the early, MCI stage, rather than the dementia stage, will allow healthcare professionals to intervene sooner – and at a stage that makes a great difference in people’s lives.
Preclinical AD
Evidence of Alzheimer's in the brain, but no symptoms
MCI due to AD
Mild symptoms but independence is maintained
Mild AD dementia
Symptoms interfere with more complex activities and independence is no longer maintained
Moderate to severe AD dementia
Cognitive and functional symptoms interfere with many to most activities and lead to progressive loss of independence
Understanding signs of normal aging vs. Alzheimer’s disease
View Full TableUnderstanding signs of normal aging vs. Alzheimer’s disease
AD affects memory, behavior, problem-solving and daily activities. It’s a medical condition – not part of normal aging – and one of the biggest public health challenges of our time. View the table below to compare normal signs of aging and Alzheimer’s.
AD affects memory, behavior, problem-solving and daily activities. It’s a medical condition – not part of normal aging – and one of the biggest public health challenges of our time. View the table below to compare normal signs of aging and Alzheimer’s.
Normal aging |
Alzheimer's |
| Occasionally making poor decisions | Frequently making poor decisions and having poor judgment |
| Occasional errors with managing finances | Trouble keeping track of bills and concentrating |
| Occasionally needing help with daily tasks | Difficulty completing daily tasks |
| Getting confused about what day of the week it is, but remembering it later | Confusion about place and time, including losing track of dates and sometimes forgetting where you are and how you got there |
| Having difficulty finding the right word once in awhile | Struggling with vocabulary, as well as trouble joining or following a conversation |
| Occasionally misplacing items, but having the ability to retrace steps and find them | Misplacing items, but losing the ability to retrace steps to find them |
| Lack of interest in social and familial obligations from time to time | Withdrawal from work, hobbies and social obligations |
| Irritability when a routine is disrupted | Changes in personality and mood, including getting easily upset |
| Changes with vision, which can be related to cataracts | Difficulty understanding visual images and spatial relationships |
| Forgetting appointment or names once in a while, but remembering them afterwards | Forgetting recently learned information and asking for the information repeatedly or relying on others for things previously handled on one's own |
Jeff’s Story: An Alzheimer’s Diagnosis
Jeff’s Story: Being diagnosed with Alzheimer’s
After a series of misdiagnoses, he’s now battling cognitive decline with grace and courage.
Read his story
References
- Alzheimer’s Association. 2024 Alzheimer’s Disease Facts and Figures. Alzheimer's Dement 2024;20(5).
- Alzheimer’s Association. Accessed July 1, 2023.
- Sabbagh MN, Lue LF, Fayard D, Shi J. Increasing Precision of Clinical Diagnosis of Alzheimer's Disease Using a Combined Algorithm Incorporating Clinical and Novel Biomarker Data. Neurol Ther. 2017 Jul;6(Suppl 1):83-95
- Elecsys® Method Sheets: ms_08846634501; ms_08821909501; ms_08846715501; ms_08846693501; ms_08821941501.