Building on a decade of research, a team led by Clifford Jack, M.D. has published new, comprehensive criteria for Alzheimer's diagnosis and research. Based on 2011 diagnostic guidelines and 2018 research framework, the 2024 criteria aim to enhance diagnostic confidence, early detection, and standardization of research and care.

How and Why New Criteria are Being Implemented 

The revised criteria for diagnosis and staging of Alzheimer's Disease were devised with various core principles in mind. Primarily, they are designed to define Alzheimer’s based on biology rather than clinical syndrome. Furthermore, they acknowledge Alzheimer’s as “a continuum that begins with the appearance of changes in the brain associated with the disease processes in asymptomatic individuals.” Notable progression through stages defined by the criteria includes hallmarks of increasing levels of disease-related brain changes that result in clinical symptoms. At this point, an Alzheimer’s Disease diagnosis can confidently be made in an individual with abnormal core biomarkers.

These criteria have seen several iterations over the years and draw on aspects of other impactful guidelines outlining best practices for clinical and research reporting. The guidelines set forth by the National Institute on Aging (NIA) in 2011 and 2012 focused on the key three stages of Alzheimer's disease: preclinical Alzheimer's, mild cognitive impairment (MCI) due to Alzheimer's, and dementia due to Alzheimer's.

With these stages defined, researchers and clinicians are recommended to:

  • Rank the severity of Alzheimer's pathology by examining three primary changes.
  • Notate these evaluations as "Alzheimer's disease neuropathologic changes," regardless of whether the individual was diagnosed with Alzheimer's while alive, aiming to comprehend the complete spectrum of brain alterations that may happen in people with or without Alzheimer's symptoms.
  • Incorporate the examination of Lewy bodies, vascular irregularities, and other brain changes that frequently occur alongside Alzheimer's indicators.

Many of these same principles have been carried over to the new criteria published on June 27, 2024 in Alzheimer’s & Dementia®: The Journal of the Alzheimer’s Association.

Outlining Core Biomarkers 

The new guidelines emphasize several core biomarkers, particularly tau antibodies. Key biomarkers include CSF or plasma-based amyloid-β (Aβ)42; phosphorylated tau (p-tau) variants such as p-tau 217, 181, and 231 in CSF or plasma; tau PET scans; and CSF or plasma microtubule-binding region (MTBR)-tau 243, among other phosphorylated and non-phosphorylated tau forms.

These tau-focused biomarkers are recommended for diagnosing, staging, and determining the prognosis of Alzheimer's disease and for evaluating treatment effectiveness. Tau biomarkers include: Plasma p-tau 217, the p-tau 217 ratio, and CSF p-tau 181/Aβ42, total-tau/Aβ42, and Aβ42/40. Additionally, tau PET, MTBR-tau 243 in CSF or plasma, and other tau forms are also valuable for staging, prognosis, and treatment assessment.

Conceptual biological staging with fluid biomarkers: This table shows the staging of AD using biomarkers. Initial-stage biomarkers include p-tau181 and AB42 (beta-amyloid 42) ratios.

The guidelines published by Jack and his team suggest that “abnormality on specific Core 1 biomarkers is sufficient to diagnose AD.” More specifically, it proposes that amyloid PET, CSF Aβ 42/40, CSF p-tau 181/Aβ 42, or CSF t-tau/Aβ 42 can be used to diagnose Alzheimer’s Disease. Additional diagnostic options include “‘accurate’ plasma assays where ‘accurate’ can be defined as accuracy that is equivalent to approved CSF assays in detecting abnormal amyloid PET in the intended-use population.” 

Sourcing p-Tau Antibodies

The new criteria for the diagnosis and staging of Alzheimer’s Disease are a welcome guideline for both researchers and companies developing assays to detect p-tau 217, 181, and 231. They offer recommendations on which biological reagents and life science products are most valuable in conducting neurodegenerative disease research, but research teams still need to identify reagent suppliers with highly reproduceable and well-tested antibodies.

Archetypical sequence of biomarker changes: This graph represents changes in biomarkers over time. The pink “N” represents neurological function decline, and abnormal biomarker levels can clearly be detected well before neurodegenerative decline begins. 

The new criteria for the diagnosis and staging of Alzheimer’s Disease are a welcome guideline for both researchers and companies developing assays to detect p-tau 217, 181, and 231. They offer recommendations on which biological reagents and life science products are most valuable in conducting neurodegenerative disease research, but research teams still need to identify reagent suppliers with highly reproduceable and well-tested antibodies.

ICL manufactures a wide variety of reliable, research-ready antibodies, including p-tau 217, 181, and 231. Our reagents are designed with research and in vitro diagnostics in mind, ensuring reproducibility and clean results on vital Alzheimer’s research.

With so many lives affected by Alzheimer’s, early and effective diagnosis can make all the difference, and the new criteria published by NIA and the Alzheimer's Association provide a strong foundation for the implementation of biotechnology that can do just that.

Learn more about how ICL can support your research and IVD projects by scheduling a call with our sales team today.