TABLE 1.

Summary of AD biomarker methods

Table 1. (A) Neuroimaging AD biomarkers
PET
Amyloid PET: Quantification of amyloid plaque deposition (A)
Tracers	Quantification	Interpretation
[11C]Pittsburgh compound‐B (PiB) [18F]Florbetapir (Amyvid) [18F]Flutemetamol (Vizamyl) [18F]Florbetaben (Neuraceq)	Amyloid quantified in comparison to a reference brain region, deriving DVR or SUVR Typical reference regions include Cerebellum (gray and/or white matter), pons, or subcortical white matter	Global or regional amyloid burden

Tau PET: Quantification of neurofibrillary tangles (T)
Tracers	Quantification	Interpretation
[18F]Flortaucipir (Tauvid) [18F]MK‐6240 [18F]RO‐948 [18F]PI‐2620 [18F]GTP1	Tau quantified in comparison to a reference brain region, deriving DVR or SUVR Typical reference regions include Cerebellum (gray and/or white matter), pons or subcortical white matter	Global or regional tau tangle pathology

FDG‐PET: Quantification of hypometabolism, synaptic dysfunction, metabolic dysfunction, neuronal cell loss (N)
Tracers	Quantification	Interpretation
[18F]Fluorodeoxyglucose (FDG)	Cerebral glucose uptake/metabolism SUV or SUVR Images typically normalized to: Cerebellum, pons, whole brain/global signal	Hypometabolism is typically interpreted as neurodegeneration (especially synaptic loss)

MRI
MRI volume: Quantification of atrophy or neurodegeneration (N)
Technique	Interpretation
T1‐weighted MRI	Gray matter, white matter, and CSF volumes used to index atrophy Regional atrophy assessed by examining volume at the voxel or vertex‐level, or volume of segmented structures (eg, hippocampus) in reference to total brain or intracranial volume Cortical thickness/thinning
Diffusion‐weighted MRI	Exploits Brownian motion of water molecules to assess subtle cortical and subcortical neurodegeneration

MRI Measurement of cerebrovascular dysfunction. Not directly related to AT(N) criteria
Technique	Interpretation
T2FLAIR MRI to assess WMH Arterial spin labelling perfusion MRI	Marker of small vessel disease Marker of capillary flow
4D Flow Susceptibility‐weighted MRI	Blood flow and pulsatility within intracranial arteries Cerebral microbleeds

Table 1 (B) CSF AD biomarkers
CSF Aβ: Quantification of amyloid proteins in CSF (A)
Proteins	Detection methods	Interpretation
Aβ40 Aβ42	Immunoassays Mass spectrometry	Lower levels of Aβ42 and reduced Aβ42/Aβ40 ratio suggest deposition in brain tissue, that is, AD neuropathology

CSF tau: Quantification of tau proteins in CSF (T)
Proteins	Detection methods	Interpretation
T‐tau P‐tau181 P‐tau217 P‐tau231	Immunoassays Mass spectrometry	Higher levels of tau proteins suggest Aβ pathology‐induced neuronal tau phosphorylation and secretion, that is, AD‐type tau pathophysiology

Various other proteins measured in CSF (N)
Proteins	Detection methods	Interpretation
NfL Neurogranin (Ng) Chitinase‐3‐like protein 1 (YKL‐40) Glial fibrillar acidic protein (GFAP)	Immunoassays Mass spectrometry	Axonal degeneration (NfL) Synaptic dysfunction and degeneration (Ng) Neuroinflammation/astrocytic activation (YKL‐40, GFAP)

Table 1 (C). Plasma AD biomarkers
Plasma Aβ: Quantification of amyloid proteins in plasma (A)
Proteins	Detection methods	Interpretation
Aβ40 Aβ42	Single molecule array (SIMOA) IP‐MS	Lower levels of Aβ proteins suggestion deposition in brain tissue, that is, AD neuropathology

Plasma tau: Quantification of tau proteins in plasma (T)
Proteins	Detection methods	Interpretation
T‐tau P‐tau181 P‐tau217	Single molecule array (SIMOA) IP‐MS	Higher levels of tau proteins suggestion deposition in brain tissue, that is, AD neuropathology

Various other proteins measured in plasma (N)
Proteins	Detection methods	Interpretation
NfL Glial fibrillary acidic protein (GFAP)	Single molecule array (SIMOA)	Axonal degeneration (NfL) Neuroinflammation/astrocytic activation (GFAP)

Abbreviations: Aβ, amyloid beta; AD, Alzheimer's disease; AT(N) criteria, National Institute on Aging–Alzheimer's Association Research Framework with (A) amyloid beta deposition, (T) tau hyperphosphorylation or tangle formation, and (N) neuronal death; CSF, cerebrospinal fluid; DVR, distribution volume ratio; IP‐MS, immunoprecipitation mass spectrometry; MRI, magnetic resonance imaging; NfL, neurofilament light; PET, positron emission tomography; p‐tau181/217/231, tau phosphorylated at threonine 181/217/231; SUV, standardized uptake value; SUVR, standardized uptake value ratio; t‐tau, total tau; WMH, white matter hyperintensities.