Table 2.

ATN classification of neurodegenerative disorders including those related to Alzheimer’s disease (AD). The three categories most relevant to clinical trials for AD are shaded. The type of trial associated with each group in the classification is noted.

Amyloid (A)	Tau (T)	Neurodegeneration (N)	Comment	Trial Population
Negative	Negative	Negative	Normal	Primary prevention trials; before amyloid is present
Positive	Negative	Negative	Alzheimer pathology; this defines preclinical AD before any changes associated with amyloid have begun	Secondary prevention trials; amyloid is present, tau is not; delay of tau spread as a potential outcome
Positive	Positive	Negative	AD; amyloid and tau changes are present; no effect on neurodegeneration	Secondary prevention trials; amyloid and tau are present, neurodegeneration is not; delay in tau spread or development of neurodegeneration are potential outcomes
Positive	Positive	Positive	AD; amyloid, tau, and neurodegeneration	Treatment trials; all 3 basic biomarkers are present; slowing of progression or delay to milestone are appropriate designs
			This category will also include mixed dementia where AD co-exists with other brain disorders such as cerebrovascular disease. Comorbid conditions contribute to the neurodegeneration component.	Combination treatment trials could include this population; for example, trials including AD and CVD
Positive	Negative	Positive	Alzheimer pathology plus some other cause of neurodegeneration	Combination treatment trials of anti-amyloid agent and drugs addressing concomitant pathology may be warranted
Negative	Negative	Positive	Not AD; neurodegeneration only	Non-AD trials such as VaD, FTD, PSP, CBD
Negative	Positive	Negative	Not AD; elevated tau without neurodegeneration	Non-AD trials of CVD, prion disease, or early tauopathies
Negative	Positive	Positive	Not AD; elevated tau and neurodegeneration	Non-AD trials of VaD or prion disease

CBD – corticobasal degeneration; CVD – cerebrovascular disease; FTD – frontotemporal dementia; PSP – progressive supranuclear palsy; VaD – vascular dementia