Blood-based Biomarkers For Alzheimer’s Disease Diagnostics Pipeline Prospects And Future Outlook

Report Overview

Currently, Alzheimer’s disease (AD) is diagnosed using biomarkers that rely on expensive and invasive techniques, such as positron emission tomography (PET), tau-PET scans, and lumbar punctures to collect cerebrospinal fluid (CSF). Less invasive methods, like measuring brain atrophy via MRI, often lack accuracy. In contrast, blood-based biomarkers (BBBMs) offer the potential for simpler, non-invasive detection through routine blood tests at a doctor's office or lab. While still primarily used for research, blood-based tests could soon become a clinical reality once technical standards-such as normality thresholds and lab protocols-are established. This shift would empower general practitioners to diagnose AD earlier, reducing reliance on costly diagnostic procedures and potentially ensuring insurance coverage.

As noted by Prof. Giovanni Frisoni, director of the HUG Memory Centre, implementing BBBMs in general practice could significantly lower the need for complex diagnostic exams, reduce healthcare costs, and improve patient outcomes. PET and CSF biomarkers are currently approved and widely used in research for AD diagnosis, but the routine use of PET scans and lumbar punctures is limited due to the specialized expertise and infrastructure required. Only 2% of dementia patients in the UK, for example, undergo these procedures, as they are often viewed as invasive. Blood-based biomarkers are emerging as a critical tool for improving dementia diagnosis by accelerating the diagnostic process. These blood tests for Alzheimer’s disease have undergone extensive research and proven to be accurate in identifying Alzheimer’s and distinguishing it from other dementia-causing conditions. However, in the UK, there is not yet enough evidence to implement these blood tests within the NHS, as they have not been thoroughly tested across diverse patient groups. For these tests to be integrated into clinical practice, they must demonstrate the same level of sensitivity and specificity as the CSF tests currently used by the NHS. The "Blood Biomarker Challenge" aims to gather the necessary evidence to prove the accuracy of blood tests for dementia-related diseases in UK patients with suspected dementia. Equally important is ensuring that these tests can be effectively incorporated into the NHS healthcare system. More research is essential before blood-based biomarkers are ready for clinical application in the UK.

Blood-based Biomarkers for Alzheimer’s Disease Diagnostics Pipeline Prospects and Future Outlook

Comprehensive overview of the blood-based biomarkers in Alzheimer’s disease: methods, correlations, and implications.

Note:- This Table provides a detailed summary of key biomarkers relevant to Alzheimer’s disease, including Aβ42/Aβ40 ratio, phosphorylated tau protein variants, neurofilament light protein, and glial fibrillary acidic protein. Each biomarker is accompanied by its detection methods, primarily mass spectrometry and immunoassays, and remarks on its significance in Alzheimer’s pathology.

Summary of evidence and commercial status of plasma Ab42/40 and pTau assays developed by commercial entities

Blood-based biomarkers hold immense potential for AD management, as routine blood draws can be easily conducted in primary care settings. In October 2023, the Alzheimer's Association (AA) workgroup proposed that "accurate" BBBMs, which match the precision of CSF biomarkers, could be sufficient for AD diagnosis. This opens the door for blood-based diagnostics to be accepted for AD detection even before symptoms appear.

A recent study highlighted that if specialist referrals required a positive BBBM test alongside cognitive assessments, wait times for AD treatment could drop from 50 months to just 12 months. Introducing BBBMs as part of regular health screenings for older adults, particularly those at higher risk due to family history, could enable early detection and intervention. BBBMs could also enhance treatment decision-making, as the first FDA-approved amyloid-targeting treatments require confirmation of amyloid pathology before initiation. Currently, amyloid pathology is confirmed via PET scans or CSF testing, but the introduction of highly accurate BBBMs could streamline this process, reducing the burden on healthcare systems and improving patient care.

Furthermore, BBBMs may provide more efficient and quantifiable measures of treatment efficacy than traditional cognitive assessments, supporting the future of Alzheimer’s therapy.

Key Strategic Activities Undertaken By Major Players

Reimbursement Scenario

Alzheimer’s Disease Research, a program of the BrightFocus Foundation, provided early grant support for the first commercially available Alzheimer’s blood test: C2N’s PrecivityAD test, which launched in the U.S. in late 2020. Physicians in 49 states, Puerto Rico, and the District of Columbia can order the test, which costs $1,200. While it is not yet covered by private or public insurance (such as Medicare and Medicaid), C2N Diagnostics offers financial assistance options. In June 2024, C2N expanded access to the PrecivityAD test by partnering with Mayo Clinic Laboratories, making the test available worldwide.

Another blood test, Quest Diagnostics’ AD-Detect Amyloid Beta 42/40 test, was introduced in May 2022 at a cost of $500. Covered by certain insurance plans, this test measures amyloid-beta levels in the blood and must be ordered by a physician. Quest Diagnostics also developed an at-home version for individuals with a family history of Alzheimer’s or evidence of mild cognitive impairment. However, this test is not a definitive diagnostic tool, and results should be reviewed with a healthcare provider.

C2N’s PrecivityAD2 test, launched in August 2023, builds on its predecessor by measuring both amyloid-beta and tau, making it the only commercially available blood test that assesses both biomarkers.

Additionally, ALZpath developed the first blood test to measure pTau217, a specific form of tau protein linked to Alzheimer’s. Early 2024 findings confirmed the accuracy and reliability of this test, which is now available for clinical use under the name ALZpath Dx. More blood tests measuring tau are currently under development, further advancing Alzheimer’s diagnostics.

Taking Alzheimer’s blood testing into primary care 

Experts have outlined several practical steps to integrate Alzheimer’s blood tests into primary care, emphasizing that a comprehensive approach is necessary for patients to benefit fully. Among these experts is Dr. Doug Galasko, a neurologist and Alzheimer’s clinician at the University of California, San Diego, and a long-time member of the BrightFocus Alzheimer’s Disease Research Scientific Review Committee.

Dr. Galasko stresses that Alzheimer’s blood tests should be used alongside cognitive testing, which he refers to as a “vital sign” of brain health. However, he notes that many primary care physicians may lack the time or expertise to consistently perform cognitive assessments. He also cautions that Alzheimer’s blood tests are not simple or routine, requiring physicians to have discussions with patients about the test's purpose, context, and possible outcomes before ordering it. After receiving the results, in-depth conversations regarding the interpretation, prognosis, and treatment options must take place. To assist with this, companies like C2N offer training and one-on-one consultations for physicians using their PrecivityAD blood test, helping them interpret and share results with patients.

Dr. Galasko also points out that many primary care doctors, and even some dementia specialists, may not currently be equipped to provide the detailed analysis and discussions required for Alzheimer’s blood tests. Therefore, physicians who believe their patients would benefit from such tests need to be well-prepared in advance to offer optimal care.

In conclusion, while Alzheimer’s blood tests are becoming more accessible in the U.S., experts urge caution in their use. Patients interested in these tests should consult their doctors. If the doctor is not comfortable administering the test, they may refer the patient to a memory clinic or Alzheimer’s Disease Research Center where such tests are available. Alternatively, patients can explore participation in clinical trials that utilize Alzheimer’s blood tests for screening.