Headline change
Amyloid and tau PET are now deemed appropriate for determining eligibility and monitoring response to approved amyloid-targeting therapies.
Bedside action
When evaluating patients for new amyloid-targeting therapies, integrate amyloid PET and potentially tau PET into your diagnostic and monitoring strategy as per the updated criteria.
The Alzheimer’s Association (AA) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) have released updated Appropriate Use Criteria (AUC) for amyloid and tau PET. This comprehensive update reflects significant advancements in Alzheimer's disease diagnostics and the emergence of amyloid-targeting therapies, providing crucial guidance for clinicians navigating this evolving landscape.
Versus the Previous Version
The 2025 AUC significantly updates the 2013 amyloid PET guidelines, notably incorporating tau PET for the first time and adapting to the advent of disease-modmodifying Alzheimer's therapies.
Tau PET Use
Previous version
The prior 2013 guideline did not address tau PET imaging, as it was not yet clinically available.
This version
This guideline introduces AUC for tau PET, recognizing its role in assessing tau pathology and informing prognosis, especially in combination with amyloid PET.
Clinical impact Clinicians now have expert recommendations for when and how to utilize tau PET, expanding diagnostic capabilities beyond amyloid imaging.
Therapy Eligibility
Previous version
The 2013 guideline did not consider amyloid PET for determining eligibility for disease-modifying therapies, as none were approved.
This version
Amyloid PET is now highly appropriate for determining eligibility for approved amyloid-targeting therapies, a critical step in patient management.
Clinical impact Amyloid PET is now a standard tool for identifying candidates for new Alzheimer's treatments, directly impacting treatment access and patient selection.
Therapy Monitoring
Previous version
The 2013 guideline did not address monitoring response to amyloid-targeting therapies.
This version
Amyloid PET is moderately appropriate for monitoring response to approved amyloid-targeting therapies, as it can measure plaque removal.
Clinical impact Serial amyloid PET scans can now guide treatment duration and assess the effectiveness of amyloid-lowering interventions.
Young-Onset Dementia
Previous version
The 2013 guideline stated amyloid PET is appropriate for patients with atypically young-onset dementia (usually <= 65 years).
This version
Amyloid PET is highly appropriate for patients younger than 65 years presenting with MCI or dementia where AD pathology is suspected, with tau PET also being moderately appropriate.
Clinical impact The recommendation for young-onset dementia is reinforced, with the addition of tau PET as a valuable diagnostic tool in this population.
MCI Prognosis
Previous version
The 2013 guideline stated that the use of amyloid PET to predict the trajectory of cognitive decline in MCI was not appropriate due to limited evidence.
This version
Amyloid PET is moderately appropriate to inform the prognosis of patients presenting with MCI due to clinically suspected AD pathology, with robust evidence supporting its predictive value.
Clinical impact Amyloid PET can now be used to counsel MCI patients and families on the likelihood of progression to AD dementia, aiding future planning.
Asymptomatic Individuals
Previous version
The 2013 guideline stated that the clinical use of amyloid PET in asymptomatic individuals was inappropriate.
This version
Amyloid PET is rarely appropriate for cognitively unimpaired individuals not at increased risk for AD, and moderately confident that it is rarely appropriate for those at increased risk.
Clinical impact The guideline maintains a strong stance against routine amyloid PET in asymptomatic individuals, even those at increased risk, due to uncertain clinical utility and lack of proven preventive therapies.
Practice Notes
These practice notes highlight critical considerations for integrating amyloid and tau PET into your clinical workflow.
Stop doing this
Do not use amyloid or tau PET for nonmedical purposes.
These scans are rarely appropriate for legal, insurance, or employment screening, as they do not provide information on functional impairment and AD pathology can be present in cognitively unimpaired individuals.
Caution
Be cautious when interpreting positive amyloid PET in older, cognitively unimpaired individuals.
Amyloid positivity increases with age, and a positive scan alone does not guarantee future cognitive decline or AD diagnosis, especially in the absence of symptoms.
Implementation
Ensure comprehensive clinical evaluation precedes PET imaging.
Amyloid or tau PET should not substitute for a detailed medical history, neurobehavioral assessment, physical exam, and other diagnostic tests to rule out reversible causes of cognitive impairment.
Shared decision point
Engage in shared decision-making with patients and families.
Discuss the potential benefits, risks, and financial implications of PET scans, including the 'value of knowing' and the possibility of indeterminate results, to align with patient preferences.
Monitoring
Do not use amyloid PET to track disease severity or progression.
Amyloid accumulation plateaus early in AD, and serial amyloid scans do not provide actionable information on disease severity or progression; clinical evaluations are more appropriate.
Special population
Avoid using PET scans as a substitute for genetic testing in suspected autosomal dominant AD.
PET scans cannot confirm the presence of DIAD mutations, and genetic counseling and testing remain the standard of care for these cases.
Key Recommendations
The following key recommendations outline the appropriate use of amyloid and tau PET imaging across various clinical scenarios, emphasizing their role in diagnosis, prognosis, and therapeutic decision-making in Alzheimer's disease.
Key recommendations14 highlighted
01
In cognitively unimpaired individuals not at increased risk for AD based on age, APOE4 genotype, or family history, do not use amyloid PET.
Line / Strength1 Highly confident that the use of the tracer is rarely appropriate.
EvidenceAmyloid PET-positive CU individuals show accelerated cognitive decline, but significant uncertainty remains about individual cognitive outcomes, and many do not develop clinically meaningful impairment. The uncertain clinical utility outweighs benefits without proven preventive therapies.
Avoid amyloid PET in low-risk, asymptomatic individuals; focus on clinical assessment.
This judgment may change with the availability of proven preventive therapies.
p. 12 · Clinical Scenario 1
02
In cognitively unimpaired individuals at increased risk for AD based on age, APOE4 genotype, or family history, do not use tau PET.
Line / Strength1 Highly confident that the use of the tracer is rarely appropriate.
EvidenceCurrently available information on tau PET utility in this scenario is limited. The probability of meaningfully elevated tau outside the medial temporal lobe is very low in CU individuals, even with risk factors.
Tau PET is not recommended for asymptomatic individuals, even those with AD risk factors.
Research is ongoing to better understand tau PET utility in this population.
p. 13 · Clinical Scenario 2
03
In patients younger than 65 years presenting with MCI or dementia where AD pathology is suspected, use amyloid PET.
Line / Strength9 High confidence that use of the tracer is appropriate.
EvidenceAmyloid PET is highly accurate in detecting AD neuropathology in young-onset impairment, where rates of amyloid positivity are lower in CU people or other neurodegenerative syndromes. It helps rule in AD as the underlying pathology, especially given the greater frequency of atypical presentations.
Prioritize amyloid PET for younger patients with suspected AD to confirm pathology and guide management.
Consider lower frequency of coexisting pathologies in young-onset AD brains.
p. 14 · Clinical Scenario 5
04
In patients younger than 65 years presenting with MCI or dementia where AD pathology is suspected, consider tau PET.
Line / Strength8 Moderately confident that use of the tracer is appropriate.
EvidenceTau PET can help detect AD pathology in young-onset AD, often showing higher intensity and spatial spread. Patients are more likely to be in advanced Braak stages, increasing the likelihood of a positive tau PET scan. Variability in tau PET patterns mirrors neurodegeneration.
Tau PET can provide additional diagnostic clarity and staging information in younger AD patients.
Recommendations are based on current evidence, which is still evolving.
p. 14 · Clinical Scenario 5
05
In patients 65 years or older presenting with MCI or dementia syndrome consistent with AD pathology (amnestic presentation), consider amyloid PET.
Line / Strength8 Moderately confident that use of the tracer is appropriate.
EvidenceAmyloid PET can reduce diagnostic uncertainty, as 15%-20% of clinically diagnosed late-onset probable AD dementia cases have negative amyloid PET. A negative scan rules out AD pathology, while a positive scan increases confidence and can reduce the need for further testing.
Use amyloid PET to confirm or rule out AD pathology in older patients with typical amnestic presentations, guiding further workup.
Prevalence of amyloid PET positivity decreases with older age in typical amnestic dementia due to other pathologies.
p. 14 · Clinical Scenario 6
06
In patients presenting with MCI or dementia syndrome that could be consistent with AD pathology but has atypical features, consider amyloid PET.
Line / Strength8 Moderately confident that use of the tracer is appropriate.
EvidenceAmyloid PET is helpful in excluding AD neuropathology in patients with atypical features (e.g., non-amnestic, rapid/slow progression, mixed etiology). A negative scan suggests non-AD processes, while a positive one increases the likelihood of AD as primary or contributing pathology.
Utilize amyloid PET to clarify diagnosis in complex or atypical dementia presentations, guiding differential diagnosis.
Patient's age should be considered due to increasing amyloid prevalence in CU individuals with age.
p. 15 · Clinical Scenario 7
07
In patients with an established biomarker-supported diagnosis of MCI or dementia due to AD pathology, do not use amyloid PET to determine disease severity or track progression.
Line / Strength1 Highly confident that the use of the tracer is rarely appropriate.
EvidenceAmyloid accumulation plateaus at the stage of mild AD dementia, and serial scans do not provide actionable information on disease severity or progression. There is little correlation between brain amyloid levels and cognitive function in MCI or AD.
Avoid repeat amyloid PET scans in patients with established AD diagnosis for monitoring purposes.
Disease severity and progression should be tracked by clinical evaluation and cognitive testing.
p. 15 · Clinical Scenario 8
08
In patients with MCI or dementia who have equivocal or inconclusive results on recent CSF biomarkers, consider amyloid PET.
Line / Strength8 Moderately confident that use of the tracer is appropriate.
EvidenceIn cases where CSF Ab42/Ab40 and P-tau/Ab42 biomarker ratios are very close to established cutoffs, amyloid PET can help determine Ab status more confidently. While CSF assays measure soluble forms, PET characterizes the magnitude and spatial distribution of fibrillar amyloid.
Use amyloid PET to resolve diagnostic uncertainty when CSF biomarker results are ambiguous.
Amyloid PET offers additional information beyond CSF, but this information may not always lead to changes in diagnosis or management.
p. 17 · Clinical Scenario 11
09
In patients presenting with MCI due to clinically suspected AD pathology, consider amyloid PET to inform prognosis.
Line / Strength8 Moderately confident that use of the tracer is appropriate.
EvidenceRobust evidence shows amyloid PET predicts future outcomes in MCI; a majority with positive scans progress to AD dementia, while risk is significantly lower for amyloid-negative individuals. A positive scan is associated with an average hazard ratio of 3–4 for conversion to dementia.
Utilize amyloid PET to provide prognostic information to MCI patients and families, aiding future planning.
Individual rates of clinical progression are highly variable, and prognostic value may improve when combined with MRI or FDG PET.
p. 17 · Clinical Scenario 12
10
In patients presenting with dementia due to clinically suspected AD pathology, consider tau PET to inform prognosis.
Line / Strength7 Only somewhat confident that the use of the tracer is appropriate.
EvidenceNeurofibrillary tangle burden correlates more closely with dementia severity than amyloid burden. Tau PET strongly correlates with longitudinal decline in cognitive scores (e.g., MMSE) in amyloid-positive AD dementia.
Tau PET can offer insights into the severity and potential progression of dementia in suspected AD cases.
Limited available data; more research is needed to fully establish its prognostic value.
p. 18 · Clinical Scenario 13
11
In patients being evaluated for treatment with an approved amyloid-targeting therapy, use amyloid PET to determine eligibility.
Line / Strength9 High confidence that use of the tracer is appropriate.
EvidenceAmyloid PET is required by FDA prescribing information and AURs for initiating approved amyloid-targeting therapies (e.g., lecanemab, donanemab). It offers high diagnostic accuracy, low variability, and information on the extent of amyloid pathology.
Amyloid PET is essential for screening patients for approved amyloid-lowering treatments.
This recommendation reflects an increase in confidence from prior ratings due to recent therapeutic advancements.
p. 18 · Clinical Scenario 14
12
In patients being evaluated for treatment with an approved amyloid-targeting therapy, consider tau PET to determine eligibility.
Line / Strength8 Moderately confident that use of the tracer is appropriate.
EvidenceBaseline tau PET may predict the magnitude of clinical benefit from amyloid removal by monoclonal antibodies. Clinical outcomes were greater in 'low-medium' tau PET groups in trials like TRAILBLAZER-ALZ2 and CLARITY-AD.
Tau PET can help identify patients most likely to benefit from amyloid-targeting therapies, particularly those at earlier stages of tau spread.
Use of tau PET for treatment eligibility is not included in FDA prescribing information or published AURs for currently approved therapies.
p. 18 · Clinical Scenario 14
13
In patients who have received an approved amyloid-targeting therapy, consider amyloid PET to monitor response.
Line / Strength8 Moderately confident that use of the tracer is appropriate.
EvidenceSerial amyloid PET scans can measure plaque removal and confirm target engagement in clinical trials. Lowering of the amyloid PET signal was a suitable surrogate biomarker for accelerated FDA approval. Treatment duration in trials like TRAILBLAZER-ALZ2 was titrated to amyloid PET response.
Amyloid PET can guide management by assessing the effectiveness of amyloid-lowering therapies and potentially determining treatment duration.
Use of amyloid PET for treatment monitoring is not included in FDA prescribing information for all approved therapies, but is for donanemab.
p. 18 · Clinical Scenario 15
14
In patients presenting with prodromal Lewy body disease or DLB, do not use amyloid PET.
Line / Strength2 Moderately confident that the use of the tracer is rarely appropriate.
EvidenceAmyloid PET is positive in over 50% of DLB patients due to high prevalence of amyloid plaques. A positive scan does not distinguish AD from DLB, and results are unlikely to influence drug treatment as acetylcholinesterase inhibitors are indicated in both.
Avoid amyloid PET for routine diagnostic evaluation of DLB due to high co-pathology and limited impact on management.
A negative amyloid PET scan can help exclude an AD diagnosis in this population.
p. 16 · Clinical Scenario 9