Importance of Autopsy Validation in AD Diagnostic Tests

The emergence of new drugs and therapies for early stage Alzheimer’s disease (AD), known as mild cognitive impairment (MCI) or mild dementia, has intensified the challenge of identifying the most appropriate, cost-effective treatment for (AD). The risk-benefit of these new disease modifying agents has raised urgency for accurate tests to verify an AD diagnosis earlier in the disease progression.

Current diagnostic tests largely measure proteins that are associated with but not necessarily causative of AD.  Without a definitive diagnosis in the early stage of the disease, however, stakeholders face a complex and expensive uphill battle in the care journey. 

The current diagnosis pathway relies on cognitive tests, imaging and invasive procedures, such as amyloid PET, MRI and CSF-based biomarkers, which have a misdiagnosis rate of 28.4%. After cognitive tests assess the degree of cognitive impairment and blood work rules out other, potentially treatable causes of dementia, clinicians must then utilize additional diagnostic testing that is fraught with error and expense, prompting payers to refuse to cover them.  Compounding the challenge of diagnosing AD in MCI or earlier stage dementia is that not all patients will progress to AD.  Data suggests that only about 39% of people with MCI progress to dementia and 33% of MCI patients progress to AD.  

Fortunately, there is good news in the form of a promising breakthrough: DISCERN™ is the first autopsy-validated, highly accurate, minimally invasive test for the definitive diagnosis of AD versus other forms of non-AD dementias and those with AD and other degenerative pathologies. DISCERN is composed of three discrete assays that accurately assess the loss of synaptic activity in the brain due to AD and has been validated through biopsy.

The Value of Autopsy Validation

DISCERN reflects 30 years of research at the National Institutes of Health (NIH) to map the molecular pathways that create memory with mechanisms that are conserved across evolution, i.e. from marine snails progressing through mammals, with confirmation provided by a collaboration with the Harvard Brain Bank. 

Furthermore, for more than a decade at the Rockefeller Neurosciences Institute, researchers conducted a series of human subject studies—culminating in autopsy-validated trials—and correlated AD-specific changes to the PKC-Epsilon cascades, which could be identified through deficiencies in skin fibroblast networks.  In these studies, patients with dementia were followed for up to eight years prior to death to validate the DISCERN test in early AD.

AD often presents with the loss of recent memory with phenotypical expression taking place in the brain, but also with pathophysiological expression peripherally. This research, which has been published in over 300 peer-reviewed papers, resulted in the development of three SDx AD biomarkers that accurately identify and distinguish AD. 

The results were validated using the NIH “gold standard” of dementia in life and autopsy confirmation of amyloid plaques and neurofibrillary tangles. In early AD (within four years of a dementia diagnosis),  DISCERN was 100% accurate versus clinical diagnosis accuracy of 50% versus this NIH standard.

It’s also important to understand that an early, accurate AD diagnosis allows patients to start appropriate clinical interventions sooner, saving time, money and the anguish of patients and caregivers not knowing what to expect medically. Early diagnosis also gives patients the chance to make decisions about their care. 

Accurate AD Test Available Today

DISCERN’s assays have demonstrated >95% sensitivity and specificity. It also identifies the AD-specific degeneration biomarker for a definitive diagnosis, differentiates AD from other non-AD dementias and identifies those with AD in addition to other degenerative pathologies. Because this new AD test assesses synaptic loss, it should be considered a tool to manage appropriate patient access to future approved therapies, in addition to the clinical and economic benefits of improved early, accurate diagnosis. 

Giving providers, patients and families a clear answer about AD helps them focus the patient journey, enables pharmaceutical companies to identify appropriate clinical trial participants and allows payers to establish protocols and prior authorizations for prescribing and reimbursing treatment. 

Because so many people are touched in some way by AD, we hope DISCERN will help guide drug discovery, development, and dosing, and, thereby, enhance peace of mind to more patients and families.