Is one core 1 biomarker, either Amyloid beta (Aβ) or Hyperphosphorylated tau (T1), sufficient for an AD diagnosis, or are both required?

According to 2025 Diagnostic Criteria: Both Core 1 Biomarkers (Amyloid Beta AND Hyperphosphorylated Tau) Are NOT Required—Either One Alone Is Sufficient

According to the 2025 Alzheimer's Association diagnostic criteria, an abnormal Core 1 biomarker result—either amyloid beta (Aβ) OR hyperphosphorylated tau (T1)—is sufficient to establish a biological diagnosis of AD. 1, 2

Understanding the Core 1 Biomarker Framework

The 2025 criteria define Core 1 biomarkers as:

• Aβ ("A"): Detected via PET, CSF, or plasma 1
• Hyperphosphorylated tau ("T1"): Specific CSF or plasma tau species including p-tau 217, p-tau 181, and p-tau 231 1

A single abnormal Core 1 biomarker (either A or T1) is sufficient to establish the diagnosis of AD and inform clinical decision-making throughout the disease continuum. 2 This represents a fundamental shift from requiring both biomarker categories.

The Biological Definition Approach

The 2025 criteria define AD as a biological process rather than purely a clinical syndrome 2. This means:

• AD diagnosis begins with the appearance of AD neuropathologic change (ADNPC), even while patients are asymptomatic 2
• Core 1 biomarkers map onto either the amyloid beta pathway OR the AD tauopathy pathway, but both reflect the presence of ADNPC more generally (neuritic plaques and tangles) 2
• An abnormal result in either pathway is sufficient because both indicate the underlying AD pathological process 2

Clinical Application Algorithm

For Establishing AD Diagnosis:

1. If amyloid biomarker (PET, CSF, or plasma Aβ42/40) is positive → AD diagnosis established 1, 2
2. If hyperphosphorylated tau biomarker (p-tau 217, p-tau 181, or p-tau 231) is positive → AD diagnosis established 1, 2
3. Either one alone is sufficient; you do NOT need both 2

For Increasing Diagnostic Confidence:

• Core 2 biomarkers (tau PET, specific CSF tau species like p-tau 205) provide prognostic information and when abnormal, increase confidence that AD is contributing to symptoms 1
• Having both Core 1 biomarkers positive increases certainty, but this is not required for diagnosis 1, 2

Important Distinction from Older Criteria

This differs significantly from earlier frameworks:

• The 2011 NIA-AA criteria suggested that for high likelihood of dementia being due to AD, biomarkers of both Aβ and neuronal injury were needed 1
• The 2025 criteria explicitly state that a single Core 1 biomarker is sufficient for AD diagnosis 2
• The older approach treated biomarkers as supportive evidence; the new approach treats them as diagnostic 2

Critical Caveats

When Both Biomarkers Are Tested:

• If both Core 1 biomarkers (Aβ AND tau) are positive: High likelihood dementia is due to AD 1
• If both are absent: Dementia is highly likely NOT due to AD 1
• If results are conflicting (one positive, one negative): Likelihood is intermediate 1

Clinical Context Matters:

• Biomarkers alone are not sufficient for confident diagnosis—they should be supplementary to clinical assessment 3
• AD biomarkers should not be used as standalone diagnostic tests for symptomatic AD, as cognitive symptoms often have multiple causes 1
• The diagnosis still requires ruling out other conditions that could substantially affect cognition 1

For Treatment Decisions:

• Positive amyloid PET is required before initiating anti-amyloid monoclonal antibody therapy 1
• In this specific context, amyloid biomarker confirmation is mandatory, though the modality (PET, CSF, or plasma) is not specified 1

Practical Implementation

For asymptomatic individuals (Stage 1): Biomarker evidence alone establishes AD diagnosis 1

For symptomatic patients (MCI or dementia):

• Clinical syndrome consistent with AD PLUS
• Either positive amyloid biomarker OR positive hyperphosphorylated tau biomarker
• Equals sufficient criteria for AD diagnosis 2

The key paradigm shift: AD is now defined by biology (presence of pathology) rather than by clinical symptoms, and a single Core 1 biomarker abnormality is the threshold for biological diagnosis 2.