CSF Biomarkers of Alzheimer’s Disease: Impact on Disease Concept, Diagnosis, and Clinical Trial Design

Table 3

Proposed NIA-AA criteria for the diagnoses of Alzheimer’s disease (AD), mild cognitive impairment due to AD, and preclinical AD.

Criteria	Biomarkers		Cognition		Diagnosis	Likelihood of AD
Alzheimer’s disease
^1Original-clinical alone	N/A				AD dementia or non-AD dementia	N/A
	Amyloid	Injury	Cognition
^2Revised-clinical + biomarkers*	+	?	AD dementia		Probable AD dementia	Intermediate
	?	+	AD dementia		Probable AD dementia	Intermediate
	+	+	AD dementia		Probable AD dementia	Highest
	+	+	Non-AD dementia		Possible AD dementia; (with atypical presentation)	High (but does not rule out second etiology)
	−	−	Non-AD dementia		Dementia (unlikely due to AD)	Lowest
Mild cognitive impairment
^3Original-clinical alone	N/A				MCI	N/A
	Amyloid	Injury	Cognition
^4Revised-clinical + biomarkers*	+	?	MCI		MCI due to AD	Intermediate
	?	+	MCI		MCI due to AD	Intermediate
	+	+	MCI		MCI due to AD	Highest
	−	−	MCI		MCI due to AD	Lowest
Preclinical Alzheimer’s disease
^5Original-clinical alone	N/A				N/A	N/A
	Amyloid	Injury	Cognition	Subtle cognitive decline
^6Revised-clinical + biomarkers**	−	−	No dementia	−	^7Stage 0/normal	N/A
	+	−	No dementia	−	Stage 1: asymptomatic cerebral amyloidosis	N/A
	+	+	No dementia	−	Stage 2: asymptomatic cerebral amyloidosis + neurodegeneration	N/A
	+	+	No dementia	+	Stage 3: asymptomatic cerebral amyloidosis + neurodegeneration + subtle cognitive/behavioral decline	N/A
	−	+	No dementia	+/−	^7SNAP (suspected non-AD pathophysiology)	N/A

McKhann et al., 1984 [7].
²McKhann et al., 2011 [14].
³Petersen et al., 1999 [62]; Petersen 2004 [63].
⁴Albert et al., 2011 [15].
⁵Not recognized as a classification.
⁶Sperling et al., 2011 [16].
⁷Jack et al., 2012 [74].
*Proposed for clinical and research use.
**Proposed for research use only.