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Table 1 Biomarkers currently in use in the AD field

From: On the path to 2025: understanding the Alzheimer’s disease continuum

Biomarker Findings in AD
– other relevant notes
CSF analysis
 Aβ1–42 Reduced concentration
– Measures soluble forms of Aβ
– Result of equilibrium shifts due to deposition/aggregation of Aβ1–42 in brain parenchyma or decreased production of Aβ1–42
– Level inversely reflects brain Aβ burden
 t-tau, p-tau Increased concentrations
– t-tau reflects the intensity of neuronal degeneration; it is elevated in other conditions such as head trauma, CJD, and stroke and therefore not specific for AD
– p-tau is a marker of the abnormal pathophysiology associated with neurofibrillary tangle pathology (hyperphosphorylation) in the brain. It is fairly specific for AD and is not elevated in primary tauopathies, head injury, or stroke
PET scana
 Amyloid PET Retention of amyloid tracer
– Amyloid tracers include 11C-PiB, florbetapir (AV-45), 91 flutemetamol (18F-PiB derivative), florbetaben (AV-1), and AZD4694
– Identifies fibrillar Aβ and provides information about extent of Aβ plaque burden in brain
 FDG PET Evidence of reduced temporo-parietal glucose metabolism
– Flurodeoxyglucose (18F) tracer
– Sensitive marker of synaptic dysfunction
 Tau PET Retention of tau tracer
– Tau tracers include flortaucipir (18 F-AV1451). Others are in development
MRI
 fMRI Measure of function
– Detects differences in BOLD signals over time and space
– Task-associated/based fMRI measures spatio-temporal changes in BOLD signal associated with administration of a task during the scan
– Resting state fMRI measures spatio-temporal correlations in intrinsic or spontaneous fluctuation of BOLD signal
– Used to study functional networks (e.g., the default mode network)
 vMRI Volume or cortical thickness reduced
– Provides a measure of volume of whole brain, specific anatomical regions, or cortical thickness
– Demonstrates medial temporal atrophy and, more specifically, hippocampal atrophy; hippocampal volume is reduced in many conditions, including old age, and several neurodegenerative disorders as well as nonneurodegenerative disorders (e.g., diabetes, sleep apnea, bipolar disorder)
  1. amyloid beta, AD Alzheimer’s disease, CSF cerebrospinal fluid, t-tau total tau, p-tau phosphorylated tau, FDG flurodeoxyglucose, PiB Pittsburgh compound B, PET positron emission tomography, MRI magnetic resonance imaging, fMRI functional MRI, vMRI volumentric MRI, BOLD blood oxygen level dependent, CJD Creutzfeldt-Jakob disease
  2. aUses specific ligands to detect AD pathophysiology in the brain