Diagnosis and biomarkers of predementia in Alzheimer's disease

Table 1 Biomarkers under investigation for Alzheimer's disease

*Correlates:*	*Method/source:*	*Alzheimer's disease-related biomarkers:*
Molecularcore neuropathology	Cerebrospinal fluid	- Concentrations of amyloid-β₄₂;
		- Total Tau and phosphorylated Tau;
	In vivo molecular imaging	- Intracerebral beta-amyloid load (e.g., PiB-PET, ¹⁸F-BAY94-9172);
		- Intracerebral aggregates of amyloid and tangle Tau(e.g., ¹⁸F-FDDNP);
Downstreamsecondary changes	Structural neuroimaging(MRI)	- Regional (medial temporal) atrophy (MRI)
		- Volumetry of hippocampus/entorhinal cortex (MRI)
		- Rate of brain/regional atrophy (MRI)
		- Voxel-based morphometry (VBM)^a
		- Diffusion tensor imaging (DTI)^a
	Functional neuroimaging(PET, SPECT, fMRI)	- Metabolic changes (FDG-PET)
		- Regional perfusion (SPECT)
		- Functional MRI^a and MRI perfusion-Functional connectivity^a
	Neurochemistry	- Proton spectroscopy (⁺H-MRS)^a
Associatedhomeostatic changes	Peripheral fluids(serum, plasma, platelets)	- Inflammatory markers (interleukins, cytokines)^a
		- Oxidative stress (isoprostanes)^a
		- Aβ40/Aβ42 ratio*;
		APP ratio^a
		- Glycogen synthase kinase-3β activity^a
		- Other markers of synaptic damage/neurodegeneration^a

^a Less validated biomarkers; Aβ, amyloid-beta peptide; APP, amyloid precursor protein; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; PET, positron emission tomography; SPECT, single-photon emission tomography; FDG, fluoro-deoxyglucose; PiB, Pittsburgh Compound B; FDDNP, 2-(1-{6-[(2-[18F]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile.

ISSN: 1741-7015